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Sökning: WFRF:(Nissbrandt Hans 1952)

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1.
  • Åberg, Maria A I, 1972, et al. (författare)
  • Risk factors in Swedish young men for amyotrophic lateral sclerosis in adulthood
  • 2018
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 265:3, s. 460-470
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16-25, n=1,819,817) who enlisted 1968-2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n=526) during up to 46years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p=0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01-1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93-0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92-0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk.
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2.
  • Fardell, Camilla, et al. (författare)
  • High IQ in Early Adulthood is Associated with Parkinson´s Disease
  • 2020
  • Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:4, s. 1649-1656
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High education level and high occupational complexity have been implicated as risk factors for Parkinson’s disease (PD). Objective: The objective was to determine whether cognitive capacity, measured as IQ, in early adulthood is associated with the subsequent development of PD. Method: Data on IQ were retrieved from the Swedish Military Service Conscription Registry, comprising Swedish males who enlisted for military service in the period 1968–1993 (N=1,319,235). After exclusion, 1,189,134 subjects in total were included in the present study. Individuals who later developed PD (N=1,724) were identified using the Swedish National Patient Register and the Swedish Cause of Death Register. Results: High education level was associated with PD. High IQ was associated with PD (p<0.0001), both when analyzed as a continuous variable and when divided into three categories. The hazard ratio for the high IQ category compared to the low IQ category was 1.35 (95% confidence interval 1.17–1.55). Strong test results on the subtests, measuring verbal, logic, visuospatial and technical abilities, were also associated with PD. In a subgroup, smoking was inversely associated with PD, as well as with IQ. Conclusions: This study identifies high IQ to be a risk factor for PD.
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3.
  • Fardell, Camilla, et al. (författare)
  • The erythrocyte sedimentation rate in male adolescents and subsequent risk of Parkinson’s disease: an observational study
  • 2021
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 1508-1516
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic inflammation may be implicated in the pathophysiology of Parkinson’s disease (PD). Since PD occurs usually in later life, most studies of causal factors are conducted in older populations, so potentially important influences from early life cannot be adequately captured. We investigated whether the erythrocyte sedimentation rate (ESR) in early adulthood is associated with the subsequent development of PD in men. As part of Swedish national conscription testing conducted from 1968 through 1983 (N = 716,550), the erythrocyte sedimentation rate, as a measure of inflammation, was measured in 659,278 young men. The cohort was observed for subsequent PD events (N = 1513) through December 2016. Cox proportional hazards models were used to estimate the hazard ratios (HR) with 95% CI with adjustment for potential confounders. Individuals with higher ESRs were significantly less likely to be diagnosed with PD, as ESR was linearly and inversely associated with PD risk. The magnitude of the association between ESR and PD risk was similar for increases up to 15mm/h, leveled off thereafter, and was non-significant for ESR values > 20mm/h. The HR for PD with basic adjustments (age at conscription, year of conscription, test center and erythrocyte volume fraction) was 0.94 (95% CI 0.89–0.99, P = 0.02) per log2 increase in ESR, corresponding to a two-fold increase in ESR. Further adjustments for potential confounders (parental education, systolic and diastolic blood pressures, and IQ) scarcely altered the HR. The results suggest a prospective association between high ESR and reduced risk for PD.
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4.
  • Landén, Mikael, 1966, et al. (författare)
  • Heart rate variability in premenstrual dysphoric disorder.
  • 2004
  • Ingår i: Psychoneuroendocrinology. - 0306-4530. ; 29:6, s. 733-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Measuring heart rate variability (HRV) is a way to assess the autonomic regulation of the heart. Decreased HRV, indicating reduced parasympathetic tone, has previously been found in depression and anxiety disorders. The objective of this study was to assess HRV in women with premenstrual dysphoric disorder (PMDD). To this end, time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle. Two variables reflecting vagal activity in the time domain, the root mean square of differences of successive normal RR intervals (rMSSD) and standard deviation of normal RR intervals (SDNN) were lower in PMDD patients, but this difference was statistically significant in the follicular phase only. The most important vagal measure in the frequency domain, supine high frequency (HF), also appeared lower in PMDD subjects during the follicular phase. It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle.
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5.
  • Wilhelmson, Anna S K, et al. (författare)
  • Testosterone is an endogenous regulator of BAFF and splenic B cell number
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibro-blastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an alpha-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
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6.
  • Ahmadi, Ahmad, et al. (författare)
  • Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
  • 2012
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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7.
  • Anderberg, Rozita H, 1976, et al. (författare)
  • Dopamine signaling in the amygdala, increased by food ingestion and GLP-1, regulates feeding behavior.
  • 2014
  • Ingår i: Physiology & behavior. - : Elsevier BV. - 1873-507X .- 0031-9384. ; 136, s. 135-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesolimbic dopamine plays a critical role in food-related reward processing and learning. The literature focuses primarily on the nucleus accumbens as the key dopaminergic target in which enhanced dopamine signaling is associated with reward. Here, we demonstrate a novel neurobiological mechanism by which dopamine transmission in the amygdala regulates food intake and reward. We show that food intake was associated with increased dopamine turnover in the amygdala. Next, we assess the impact of direct intra-amygdala D1 and D2 receptor activation on food intake and sucrose-driven progressive ratio operant conditioning in rats. Amygdala D2 receptor activation reduced food intake and operant behavior for sucrose, whereas D2 receptor blockade increased food intake but surprisingly reduced operant behavior. In contrast, D1 receptor stimulation or blockade did not alter feeding or operant conditioning for food. The glucagon-like peptide 1 (GLP-1) system, a target for type 2 diabetes treatment, in addition to regulating glucose homeostasis, also reduces food intake. We found that central GLP-1R receptor activation is associated with elevated dopamine turnover in the amygdala, and that part of the anorexic effect of GLP-1 is mediated by D2 receptor signaling in the amygdala. Our findings indicate that amygdala dopamine signaling is activated by both food intake and the anorexic brain-gut peptide GLP-1 and that amygdala D2 receptor activation is necessary and sufficient to change feeding behavior. Collectively these studies indicate a novel mechanism by which the dopamine system affects feeding-oriented behavior at the level of the amygdala.
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8.
  • Anderberg, Rozita H, 1976, et al. (författare)
  • GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality.
  • 2016
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 65, s. 54-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucagon-like peptide 1 (GLP-1), produced in the intestine and hindbrain, is known for its glucoregulatory and appetite suppressing effects. GLP-1 agonists are in clinical use for treatment of type 2 diabetes and obesity. GLP-1, however, may also affect brain areas associated with emotionality regulation. Here we aimed to characterize acute and chronic impact of GLP-1 on anxiety and depression-like behavior. Rats were subjected to anxiety and depression behavior tests following acute or chronic intracerebroventricular or intra-dorsal raphe (DR) application of GLP-1 receptor agonists. Serotonin or serotonin-related genes were also measured in the amygdala, DR and the hippocampus. We demonstrate that both GLP-1 and its long lasting analog, Exendin-4, induce anxiety-like behavior in three rodent tests of this behavior: black and white box, elevated plus maze and open field test when acutely administered intraperitoneally, into the lateral ventricle, or directly into the DR. Acute central GLP-1 receptor stimulation also altered serotonin signaling in the amygdala. In contrast, chronic central administration of Exendin-4 did not alter anxiety-like behavior but significantly reduced depression-like behavior in the forced swim test. Importantly, this positive effect of Exendin-4 was not due to significant body weight loss and reduced food intake, since rats pair-fed to Exendin-4 rats did not show altered mood. Collectively we show a striking impact of central GLP-1 on emotionality and the amygdala serotonin signaling that is divergent under acute versus chronic GLP-1 activation conditions. We also find a novel role for the DR GLP-1 receptors in regulation of behavior. These results may have direct relevance to the clinic, and indicate that Exendin-4 may be especially useful for obese patients manifesting with comorbid depression.
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9.
  • Anderberg, Rozita H, 1976, et al. (författare)
  • Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight
  • 2017
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 1062-1073
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT2A) and 5-HT2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT2A, but surprisingly not the 5-HT2C, receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation.
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10.
  • Anderberg, Rozita H, 1976, et al. (författare)
  • The Stomach-Derived Hormone Ghrelin Increases Impulsive Behavior.
  • 2016
  • Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X. ; 14, s. 1199-1209
  • Tidskriftsartikel (refereegranskat)abstract
    • Impulsivity, defined as impaired decision making, is associated with many psychiatric and behavioral disorders, such as attention-deficit/hyperactivity disorder as well as eating disorders. Recent data indicate that there is a strong positive correlation between food reward behavior and impulsivity, but the mechanisms behind this relationship remain unknown. Here we hypothesize that ghrelin, an orexigenic hormone produced by the stomach and known to increase food reward behavior, also increases impulsivity. In order to assess the impact of ghrelin on impulsivity, rats were trained in three complementary tests of impulsive behavior and choice: differential reinforcement of low rate (DRL), go/no-go, and delay discounting. Ghrelin injection into the lateral ventricle increased impulsive behavior, as indicated by reduced efficiency of performance in the DRL test, and increased lever pressing during the no-go periods of the go/no-go test. Central ghrelin stimulation also increased impulsive choice, as evidenced by the reduced choice for large rewards when delivered with a delay in the delay discounting test. In order to determine whether signaling at the central ghrelin receptors is necessary for maintenance of normal levels of impulsive behavior, DRL performance was assessed following ghrelin receptor blockade with central infusion of a ghrelin receptor antagonist. Central ghrelin receptor blockade reduced impulsive behavior, as reflected by increased efficiency of performance in the DRL task. To further investigate the neurobiological substrate underlying the impulsivity effect of ghrelin, we microinjected ghrelin into the ventral tegmental area, an area harboring dopaminergic cell bodies. Ghrelin receptor stimulation within the VTA was sufficient to increase impulsive behavior. We further evaluated the impact of ghrelin on dopamine-related gene expression and dopamine turnover in brain areas key in impulsive behavior control. This study provides the first demonstration that the stomach-produced hormone ghrelin increases impulsivity and also indicates that ghrelin can change two major components of impulsivity-motor and choice impulsivity.Neuropsychopharmacology advance online publication, 21 October 2015; doi:10.1038/npp.2015.297.
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11.
  • Andersson, Daniel, et al. (författare)
  • Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.
  • 2010
  • Ingår i: Experimental neurology. - : Elsevier BV. - 1090-2430 .- 0014-4886. ; 221:1, s. 251-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.
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12.
  • Andersson, Daniel, et al. (författare)
  • Partial depletion of dopamine in substantia nigra impairs motor performance without altering striatal dopamine neurotransmission
  • 2006
  • Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 24:2, s. 617-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous data indicate that the release of somatodendritic dopamine in substantia nigra influences motor activity and coordination, but the relative importance of somatodendritic dopamine release vs. terminal striatal dopamine release remains to be determined. We utilized simultaneous measurement of dopamine neurotransmission by microdialysis and motor performance assessment by rotarod test to investigate the effects of local dopamine depletion in rats. The vesicular monoamine transporter inhibitor tetrabenazine (100 µm) was administered locally in substantia nigra as well as in striatum. Nigral tetrabenazine administration decreased nigral dopamine dialysate concentrations to 7% of baseline and whole-tissue dopamine content by 60%. Nigral dopamine depletion was associated with a reduction in motor performance to 73 ± 6% of pretreatment value, but did not alter dialysate dopamine concentrations in the ipsilateral striatum. Striatal tetrabenazine administration decreased striatal dopamine dialysate concentrations to 5% of baseline and doubled the somatodendritic dopamine response to motor activity, but it was not associated with changes in motor performance or dopamine content in striatal tissue. Simultaneous treatment of substantia nigra and striatum reduced motor performance to 58 ± 5% of the pretreatment value. The results of this study indicate that partial depletion of nigral dopamine stores can significantly impair motor functions, and that increased nigral dopamine release can counteract minor impairments of striatal dopamine transmission.
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13.
  • Anvret, Anna, et al. (författare)
  • DJ-1 Mutations are Rare in a Swedish Parkinson Cohort.
  • 2011
  • Ingår i: The open neurology journal. - 1874-205X. ; 5, s. 8-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson's disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A
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14.
  • Anvret, Anna, et al. (författare)
  • Possible involvement of a mitochondrial translation initiation factor 3 variant causing decreased mRNA levels in Parkinson's disease.
  • 2010
  • Ingår i: Parkinson's disease. - : Hindawi Limited. - 2042-0080. ; 2010
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes important for mitochondrial function have been implicated in Parkinson's disease (PD). Mitochondrial translation initiation factor 3 (MTIF3) is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T) in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P = .0473) with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P = .0163). Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.
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15.
  • Belin, Andrea Carmine, et al. (författare)
  • Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
  • 2007
  • Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 420:3, s. 257-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
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16.
  • Bergman, Olle, 1978, et al. (författare)
  • Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease?
  • 2009
  • Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:3, s. 333-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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17.
  • Bergman, Olle, 1978, et al. (författare)
  • PITX3 polymorphism is associated with early onset Parkinson's disease.
  • 2010
  • Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:1, s. 114-117
  • Tidskriftsartikel (refereegranskat)abstract
    • PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p=0.002) or to PD patients with late onset (p=0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated.
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18.
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19.
  • Bergquist, Filip, 1970, et al. (författare)
  • Effects of local administration of L-, N-, and P/Q-type calcium channel blockers on spontaneous dopamine release in the striatum and the substantia nigra: a microdialysis study in rat.
  • 1998
  • Ingår i: Journal of neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 70:4, s. 1532-40
  • Tidskriftsartikel (refereegranskat)abstract
    • The pivotal role for voltage-sensitive calcium channels in initiating synaptic transmitter release is undisputed, but it is only partly known to what extent the different subtypes contribute in vivo. Their importance for the dendritic release of dopamine has not been investigated in vivo previously. To evaluate comprehensively the relative importance of different voltage-sensitive calcium channel subtypes for striatal dopamine release, and to further investigate the mechanism of dendritic dopamine release in the reticulate part of substantia nigra, dopamine was measured by in vivo microdialysis in the striatum or substantia nigra of awake rats. The calcium channel blockers nimodipine, omega-conotoxin-GVIA, omega-agatoxin-IVA, and neomycin were administered locally through the dialysis probes and compared with calcium-free perfusion. Results indicate that dopamine release in the striatum is mainly dependent on N- and P/Q-type channels, but the dendritic dopamine release in the substantia nigra is mediated mainly by some other calcium-dependent mechanism, for example, calcium mobilization through T-, O-, or R-type calcium channels. A portion of the dendritic release is calcium independent but can be inhibited partially by neomycin, which might suggest a role for inositol 4,5-bisphosphate breakdown products.
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20.
  • Bergquist, Filip, 1970, et al. (författare)
  • Evidence for different exocytosis pathways in dendritic and terminal dopamine release in vivo.
  • 2002
  • Ingår i: Brain research. - 0006-8993. ; 950:1-2, s. 245-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Although dendritic release was first proposed in the 1970s, the mechanism of release is still subject to debate. We have used in vivo microdialysis to study the acute effects of botulinum toxin A, B and tetanus toxin injected in the substantia nigra or striatum of freely moving rats. Spontaneous and evoked dopamine release decreased in both regions after treatment with the SNAP-25 (synaptosome-associated protein of 25 kDa) cleaving protease botulinum toxin A (1000 mouse lethal doses, MLD). Tetanus toxin (4000 MLD) did not significantly change spontaneous or evoked dopamine release in striatum or in the substantia nigra. Another synaptobrevin cleaving protease, botulinum toxin B, inhibited release in the striatum by 55% but did not affect dopamine release when injected in the substantia nigra. The results indicate that both terminal and somatodendritic dopamine release need intact SNAP-25 to occur, but somatodendritic dopamine release in contrast to terminal release depends on a botulinum toxin B resistant pathway.
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21.
  • Bergquist, Filip, 1970, et al. (författare)
  • Influence of R-type (Cav2.3) and t-type (Cav3.1-3.3) antagonists on nigral somatodendritic dopamine release measured by microdialysis.
  • 2003
  • Ingår i: Neuroscience. - 0306-4522. ; 120:3, s. 757-64
  • Tidskriftsartikel (refereegranskat)abstract
    • The release of dopamine from soma and dendrites of dopaminergic neurons in substantia nigra has been reported to be calcium-dependent, but it remains to be determined which calcium channels mediate this effect. We have used in vivo microdialysis in rat substantia nigra and striatum to investigate the effect of Ca(v)3.1-3.3 (T-type) and Ca(v)2.3 (R-type) calcium channel antagonists on somatodendritic and terminal dopamine release. Local reverse dialysis administration of 0.1-10 microM of the Ca(v)2.3 inhibitor SNX-482, or 100 microM of mibefradil, decreased the concentrations of dopamine and its metabolites in dialysate from substantia nigra, whereas 1 microM mibefradil or 40-80 microM nickel(II) induced an increase in nigral dialysate dopamine concentrations. Dopamine concentrations in striatal dialysates were decreased only by 10 microM of SNX-482 or 100 microM of mibefradil. Nickel(II) induced an increase in striatal dialysate dopamine concentration similar to that in substantia nigra. The results indicate a role for Ca(v)2.3 (R-type) voltage sensitive calcium channels in the calcium dependency of somatodendritic dopamine release, but argue against a calcium dependency mediated substantially by Ca(v)3.1-3.3 (T-type) channels.
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22.
  • Bergquist, Filip, 1970, et al. (författare)
  • Somatodendritic dopamine release in rat substantia nigra influences motor performance on the accelerating rod.
  • 2003
  • Ingår i: Brain research. - 0006-8993. ; 973:1, s. 81-91
  • Tidskriftsartikel (refereegranskat)abstract
    • The physiological role of somatodendritic dopamine release in the rat substantia nigra was evaluated with a combination of dual probe microdialysis and simultaneous motor performance tests on an accelerating rod. Three main findings support a modulating influence of somatodendritic dopamine release on motor coordination. (1) The rod performance tests were associated with an increase in extracellular dopamine but not 5-hydroxytryptamine concentrations in substantia nigra and with increases in both dopamine and 5-hydroxytryptamine concentrations in the striatum. (2) Nigral application of dopamine antagonists without intrinsic activity resulted in changed performances on the accelerating rod. The response to nigral perfusion with low concentrations (0.1, 1.0 microM) of the D(2)/D(3)-antagonist raclopride consisted of an impairment in rod performance to 63% of the pre-perfusion performance. Higher concentrations (10, 100 microM), however, were not associated with impaired rod performance, but with increased striatal dopamine concentrations. Perfusion of the substantia nigra with 1, 10 and 100 microM of the D(1)/D(5)-antagonist SCH 23390 dose-dependently impaired rod performance. SCH 23390 consistently increased dopamine and 5-hydroxytryptamine concentrations in substantia nigra but did not change the dialysate in the striatum. (3) In unilaterally 6-hydroxydopamine-lesioned rats, a dose-dependent improvement in rod performance was observed during perfusion of the substantia nigra with the non-selective dopamine agonist apomorphine.
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23.
  • Buervenich, Silvia, et al. (författare)
  • A rare truncating mutation in ADH1C (G78Stop) shows significant association with Parkinson disease in a large international sample.
  • 2005
  • Ingår i: Archives of neurology. - : American Medical Association (AMA). - 0003-9942. ; 62:1, s. 74-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. PATIENTS: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. RESULTS: The previously identified association with an ADH class IV allele remained significant (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PD patients but only in 6 controls (0.6%). This association was statistically significant (chi(2)(1) = 7.5; 2-sided P = .007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. CONCLUSION: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.
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24.
  • Carmine Belin, Andrea, et al. (författare)
  • Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian.
  • 2006
  • Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185. ; 21:10, s. 1731-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Specific variants of Leucine-rich repeat kinase 2 (LRRK2) have been shown to associate with Parkinson's disease (PD). Several mutations have been found in PD populations from different parts of the world. We investigated the occurrence of three mutations (R1441G/C/H, G2019S, and I2020T) in our Swedish case-control material and identified four carriers of the G2019S mutation in 284 PD cases and 1 95-year-old carrier in 305 controls. The other two variants were absent in our material. We conclude that the LRRK2 G2019S mutation constitutes a significant factor for PD in the Swedish population and that it is not completely penetrant.
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25.
  • Carmine Belin, Andrea, et al. (författare)
  • S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden.
  • 2007
  • Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020. ; 13:5, s. 295-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that removes ubiquitin from the C-terminal end of substrates and a component of the ubiquitin-proteasome system. A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD). We investigated the association of S18Y in our Swedish PD material. The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case-control material, supporting the hypothesis of a protective function.
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26.
  • Dickson, Suzanne L., 1966, et al. (författare)
  • The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors.
  • 2012
  • Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:14, s. 4812-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures-ventral tegmental area and nucleus accumbens-without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.
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27.
  • Eriksson, Elias, 1956, et al. (författare)
  • Escitalopram Administered in the Luteal Phase Exerts a Marked and Dose-Dependent Effect in Premenstrual Dysphoric Disorder.
  • 2008
  • Ingår i: Journal of clinical psychopharmacology. - 0271-0749. ; 28:2, s. 195-202
  • Tidskriftsartikel (refereegranskat)abstract
    • This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI.
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28.
  • Fardell, Camilla, et al. (författare)
  • S100B polymorphisms are associated with age of onset of Parkinson's disease
  • 2018
  • Ingår i: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 19:42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In this study we investigated the association between SNPs in the S100B gene and Parkinson's disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3'-UTR of the S100B gene, was strongly associated with age of onset of PD.
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29.
  • Francardo, Veronica, et al. (författare)
  • Impact of the lesion procedure on the profiles of motor impairment and molecular responsiveness to L-DOPA in the 6-hydroxydopamine mouse model of Parkinson's disease.
  • 2011
  • Ingår i: Neurobiology of disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 42:3, s. 327-40
  • Tidskriftsartikel (refereegranskat)abstract
    • 6-Hydroxydopamine (6-OHDA) lesions are being used in the mouse for basic research on Parkinson's disease and L-DOPA-induced dyskinesia. We set out to compare unilateral lesion models produced by intrastriatal or intramesencephalic injections of a fixed 6-OHDA concentration (3.2 μg/μl) in C57BL/6 mice. In the first experiment, toxin injections were performed either at two striatal coordinates (1 or 2 μl per site, termed "striatum(2 × 1 μl)" and "striatum(2 × 2 μl)" models), in the medial forebrain bundle (MFB), or in the substantia nigra pars compacta (SN) (1 μl per site). All the four lesion models produced significant forelimb use asymmetry, but spontaneous turning asymmetry only occurred in the MFB and striatum(2 × 2 μl) models. After the behavioral studies, the induction of phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) by acute L-DOPA (30 mg/kg) was used as a marker of post-synaptic supersensitivity. Striatal pERK1/2 expression was sparse in the SN and striatum(2 × 1 μl) groups, but pronounced in the striatum(2 × 2 μl) and MFB-lesioned mice. In further experiments, mice with MFB and striatal(2 × 2 μl) lesions were used to compare behavioral and molecular responses to chronic L-DOPA treatment (12 days at 3 and 6 mg/kg/day). Maximally severe abnormal involuntary movements (AIMs) occurred in all MFB-lesioned mice, whereas only 35% of the mice with striatal lesions developed dyskinesia. Striatal tissue levels of dopamine were significantly lower in the dyskinetic animals (both MFB and striatum(2 × 2 μl) groups) in comparison with the non-dyskinetic ones. Noradrenaline levels were significantly reduced only in MFB lesioned animals and did not differ among the dyskinetic and non-dyskinetic cases with striatal lesions. In all groups, the L-DOPA-induced AIM scores correlated closely with the number of cells immunoreactive for tyrosine hydroxylase or FosB/∆FosB in the striatum. In conclusion, among the four lesion procedures examined here, only the MFB and striatum(2 × 2 μl) models yielded a degree of dopamine denervation sufficient to produce spontaneous postural asymmetry and molecular supersensitivity to L-DOPA. Both lesion models are suitable to reproduce L-DOPA-induced dyskinesia, although only MFB lesions yield a pronounced and widespread expression of post-synaptic supersensitivity markers in the striatum.
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30.
  • Francardo, Veronica, et al. (författare)
  • Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism
  • 2014
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 137, s. 1998-2014
  • Tidskriftsartikel (refereegranskat)abstract
    • Sigma-1 receptor ligands may have neuroprotective and neurorestorative properties. In a mouse model of parkinsonism, Francardo et al. show that chronic treatment with the sigma-1 receptor agonist PRE-084 increases the density of striatal dopaminergic fibres and improves forelimb use. Boosting sigma-1 receptor activity may have disease-modifying effects in ParkinsonA ' s disease.The sigma-1 receptor, an endoplasmic reticulum-associated molecular chaperone, is attracting great interest as a potential target for neuroprotective treatments. We provide the first evidence that pharmacological modulation of this protein produces functional neurorestoration in experimental parkinsonism. Mice with intrastriatal 6-hydroxydopamine lesions were treated daily with the selective sigma-1 receptor agonist, PRE-084, for 5 weeks. At the dose of 0.3 mg/kg/day, PRE-084 produced a gradual and significant improvement of spontaneous forelimb use. The behavioural recovery was paralleled by an increased density of dopaminergic fibres in the most denervated striatal regions, by a modest recovery of dopamine levels, and by an upregulation of neurotrophic factors (BDNF and GDNF) and their downstream effector pathways (extracellular signal regulated kinases 1/2 and Akt). No treatment-induced behavioural-histological restoration occurred in sigma-1 receptor knockout mice subjected to 6-hydroxydopamine lesions and treated with PRE-084. Immunoreactivity for the sigma-1 receptor protein was evident in both astrocytes and neurons in the substantia nigra and the striatum, and its intracellular distribution was modulated by PRE-084 (the treatment resulted in a wider intracellular distribution of the protein). Our results suggest that sigma-1 receptor regulates endogenous defence and plasticity mechanisms in experimental parkinsonism. Boosting the activity of this protein may have disease-modifying effects in Parkinson's disease.
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31.
  • Hansson, Caroline, 1981, et al. (författare)
  • Influence of ghrelin on the central serotonergic signaling system in mice
  • 2014
  • Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 498-505
  • Tidskriftsartikel (refereegranskat)abstract
    • The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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32.
  • Henningsson, Susanne, 1977, et al. (författare)
  • Interleukin-6 gene polymorphism -174G/C influences plasma lipid levels in women.
  • 2006
  • Ingår i: Obesity (Silver Spring, Md.). - 1930-7381. ; 14:11, s. 1868-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have been associated with cardiovascular risk factors. The objective of this study was to investigate potential associations between the promoter polymorphism IL-6 -174G/C and the following indices of metabolism: BMI, waist-to-hip ratio, and plasma levels of IL-6, cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, leptin, and C-reactive protein in 252 42-year-old women and 245 51-year-old men. Subgroups were also studied 5 years later. The CC genotype of the IL-6 polymorphism was associated with lower levels of cholesterol and low-density lipoprotein (p < 0.001) in women. This finding was replicated in the follow-up, when a significant association between the CC genotype and low triglycerides was also observed. The association between the C allele and lipid pattern found in women was not found in men, where on the contrary, C carriers tended to display elevated triglycerides. IL-6 genotype was not associated with IL-6 plasma levels in either sample. The results suggest different effects of the IL-6 polymorphism on metabolic indices in women and men. None of the associations between IL-6 genotype and lipid pattern seemed to result from an effect of the polymorphism on IL-6 plasma levels.
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33.
  • Håkansson, Anna, 1978, et al. (författare)
  • Cyclooxygenase-2 polymorphisms in Parkinson's disease.
  • 2007
  • Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 144:3, s. 367-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men.
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34.
  • Håkansson, Anna, 1978, et al. (författare)
  • Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.
  • 2005
  • Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 133:1, s. 88-92
  • Tidskriftsartikel (refereegranskat)abstract
    • The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (
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35.
  • Håkansson, Anna, 1978, et al. (författare)
  • Investigation of genes coding for inflammatory components in Parkinson's disease.
  • 2005
  • Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185 .- 1531-8257. ; 20:5, s. 569-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.
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36.
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37.
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38.
  • Johansson, Annica, 1969, et al. (författare)
  • TAU haplotype and the Saitohin Q7R gene polymorphism do not influence CSF Tau in Alzheimer's disease and are not associated with frontotemporal dementia or Parkinson's disease.
  • 2005
  • Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 2:1, s. 28-35
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recent studies have described Saitohin(STH), a gene located in the human TAU gene. The corresponding protein shows a similar tissue expression to tau, which is involved in many neurodegenerative disorders including Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). A single nucleotide polymorphism in the STH gene has been suggested to be involved in sporadic AD and is in complete linkage disequilibrium with the TAU haplotype H1. OBJECTIVE: A case-control study was performed to further explore the possible involvement of the STH Q7R polymorphism and the extended TAU haplotype in AD, FTD or PD. METHODS: Patients with AD (n = 398), FTD (n = 96) and PD (n = 105), and controls (n = 186) were genotyped for the STH polymorphism and/or the TAU haplotype. Genotype data were related to levels of total-tau, phospho-tau and Abeta(1-42) in cerebral spinal fluid (CSF) in more than 300 AD patients and to an amount of senile plaques and neurofibrillary tangles in the frontal cortex and hippocampus in patients with autopsy-confirmed AD. RESULTS: The STH Q7R polymorphism and the TAU haplotype were in complete linkage disequilibrium in all patients (AD and FTD) and controls investigated for both genes. There were no significant differences in genotype or allele distributions in AD, FTD or PD cases compared to controls. Neither TAU haplotype nor STH influenced CSF levels of total-tau, phospho-tau and Abeta(1-42) significantly. In AD patients with neuropathological scores of plaque and tangles, no associations with TAU haplotype and STH were found. CONCLUSION: We found no evidence that could support a major pathogenic role of STH and TAU haplotype in AD, FTD or PD.
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39.
  • Landén, Mikael, 1966, et al. (författare)
  • Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.
  • 2007
  • Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 32:1, s. 153-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously to be effective for premenstrual dysphoric disorder (PMDD), but can be given during luteal phases only. This is of practical importance, but also of theoretical interest since it suggests that the onset of action of SRIs is shorter in PMDD than in, for example depression. In this study, both continuous and intermittent SRI administration was compared with placebo, with the special purpose of analyzing if different PMDD symptoms respond differently depending on the treatment regimen. To this end, women meeting slightly modified DSM-IV criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three menstrual cycles with paroxetine continuously, paroxetine during the luteal phase only, or placebo, the population completing at least one treatment cycle comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%. The effect size was highest for irritability (1.4) and lowest for lack of energy (0.5). Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms. The study indicates that the response rate when treating PMDD with SRIs is high, and that irritability is a key target symptom. Symptoms such as irritability, affect lability, and mood swings appear to be more inclined to respond rapidly to SRIs, enabling intermittent treatment, than are, for example, the somatic symptoms.
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40.
  • Lill, Christina M., et al. (författare)
  • The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
  • Tidskriftsartikel (refereegranskat)abstract
    • A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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41.
  • Lindgren, Hanna, et al. (författare)
  • L-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson's disease: temporal and quantitative relationship to the expression of dyskinesia.
  • 2010
  • Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 112:6, s. 1465-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract L-DOPA-induced dyskinesia in Parkinson's Disease (PD) is associated with large increases in brain dopamine (DA) levels following drug dosing, but the precise significance of this phenomenon is not understood. Here we compare DA efflux and metabolism in the striatum and the substantia nigra (SN) in dyskinetic and non-dyskinetic animals following a standard dose of L-DOPA. Rats with 6-OHDA lesions were treated chronically with L-DOPA, monitored on the abnormal involuntary movements (AIMs) scale, and then subjected to intracerebral microdialysis under freely-moving conditions. Following s.c. L-DOPA injection, peak extracellular DA levels in both striatum and SN were twice as large in dyskinetic animals compared to non-dyskinetic rats. This effect was not attributable to differences in DOPA levels or DA metabolism. The larger DA efflux in dyskinetic animals was blunted by 5-HT1A/5-HT1B receptor agonists and TTX infusion, reflecting release from serotonin neurons. Striatal levels of serotonin and its main metabolite, 5-hydroxyindolacetic acid were indeed elevated in dyskinetic animals compared to non-dyskinetic rats, indicating a larger serotonergic innervation density in the former group. High DA release was, however, not sufficient to explain dyskinesia. The AIMs output per unit concentration of striatal extracellular DA was indeed much larger in dyskinetic animals compared to non-dyskinetic cases at most time points examined. The present results indicate that both a high DA release post L-DOPA administration and an increased responsiveness to DA must coexist for a full expression of dyskinesia.
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42.
  • Niazi Shahabi, Haydeh, 1966, et al. (författare)
  • An investigation of dopaminergic metabolites in the striatum and in the substantia nigra in vivo utilising radiolabelled L-DOPA and high performance liquid chromatography: a new approach in the search for transmitter metabolites.
  • 2003
  • Ingår i: Neuroscience. - 0306-4522. ; 120:2, s. 425-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the major routes of dopamine metabolism seem to be established, at least in terminal regions such as the striatum, it is important to search for previously unknown metabolites and to investigate the relevance of previously suggested minor alternative pathways. An urgent issue is to verify and quantify the transformation of dopamine to putative toxic species, another is to further explore metabolism of dopamine located in cell bodies/dendrites, e.g. in the substantia nigra. We have developed a new method in order to widen the search for alternative metabolites of dopamine. The method is based on systemic injection of tritiated L-DOPA to rats in vivo. Brain tissue was homogenised and centrifuged and the resulting supernatant fractioned following passage through a liquid chromatography system. The radioactivity of each fraction was measured using a scintillation system. By identifying fractions containing major catecholamines and metabolites, according to a standard solution, novel metabolites can be searched for in the remaining fractions. It was possible to obtain sufficient radioactivity in separate fractions of supernatant of homogenised tissue, even from such a small brain nucleus as substantia nigra. Radioactivity was obtained in those fractions that contained the major catecholamines and their metabolites, as well as in other fractions where it may represent previously unknown metabolites of L-DOPA/dopamine. The method was used to evaluate the possibility that cytochrome P450 2E1 is involved in the metabolism of dopamine in the substantia nigra. Significant changes in the radioactivity pattern were induced by inhibition of the enzyme but conclusions about whether cytochrome P450 2E1 is involved in the metabolism of dopamine or not requires further studies. The method can be used to study the metabolism of dopamine and can be extended, by using other radiolabelled precursors, also to evaluate metabolism of other transmitters, e.g. serotonin.
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43.
  • Näslund, Jakob, et al. (författare)
  • Differences in anxiety-like behavior within a batch of wistar rats are associated with differences in serotonergic transmission, enhanced by acute sri administration, and abolished by serotonin depletion
  • 2015
  • Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 18:8, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxietyenhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxietyprone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission. Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs. Results: "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram. Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats..
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44.
  • Patil, Jaspal, et al. (författare)
  • Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1 beta and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet
  • 2016
  • Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1021-7401 .- 1423-0216. ; 23:4, s. 250-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1 beta, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxi-some proliferator-activated receptor gamma coactivator (PGC)-1 alpha in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i. p. 2 mg/kg). After 65 days, the mRNA level of IL-1 beta was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the gamma-glutamylcysteine ligase catalytic subunit (gamma GCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of gamma GCLc and Nrf2 were decreased while IL-1 beta protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3 beta (pGSK-3 beta). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1 beta protein expression in SN and elevated the mRNA level of gamma GCLc, Nrf2 protein, PGC-1 alpha protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3 beta for a long time in SN. A diet en-riched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT. (C) 2016 S. Karger AG, Basel
  •  
45.
  • Pihlstrom, L., et al. (författare)
  • Fine mapping and resequencing of the PARK16 locus in Parkinson's disease
  • 2015
  • Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 60:7, s. 357-362
  • Tidskriftsartikel (refereegranskat)abstract
    • The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinson's disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5' region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.
  •  
46.
  • Pihlstrom, L., et al. (författare)
  • Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease
  • 2013
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:6
  • Tidskriftsartikel (refereegranskat)abstract
    • enome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
  •  
47.
  • Ran, Caroline, et al. (författare)
  • No association between rs7077361 in ITGA8 and Parkinson’s disease in Sweden
  • 2016
  • Ingår i: Open Neurology Journal. - 1874-205X. ; 10, s. 25-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Integrin alpha 8 (ITGA8) encodes the alpha 8 subunit of the integrin alpha8beta1 protein and has recently been suggested as a new candidate gene for Parkinson’s disease, an age related neurodegenerative disease with unknown etiology. ITGA8 is a transmembrane protein involved in several cellular processes, such as cell adhesion, migration and cytoskeletal rearrangement. Objective: Screen a Swedish case control material for rs7077361, a genetic variant in ITGA8, in order to investigate its possible implication in Parkinson’s disease in Sweden. Method: Rs7077361 was genotyped using TaqMan quantitative Real-time PCR and tested for association using appropriate statistical methods. Results: We have screened 502 Swedish Parkinson patients and 599 healthy control individuals for rs7077361 in ITGA8. This genetic variant was in Hardy Weinberg equilibrium in the Swedish population. Allele and genotype frequencies were highly similar between the patients and controls and statistical testing showed that this genetic maker did not associate with Parkinson’s disease (p=0.67). Conclusion: Our results do not support the hypothesis of ITGA8 as a candidate gene for Parkinson’s disease in Sweden. © Ran et al.
  •  
48.
  • Ran, C., et al. (författare)
  • Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
  • 2016
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
  • Tidskriftsartikel (refereegranskat)abstract
    • Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
  •  
49.
  • Ruud, J., et al. (författare)
  • The Fat Mass and Obesity-Associated Protein (FTO) Regulates Locomotor Responses to Novelty via D2R Medium Spiny Neurons
  • 2019
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 27:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Variations in the human FTO gene have been linked to obesity and altered connectivity of the dopaminergic neurocircuitry. Here, we report that fat mass and obesity-associated protein (FTO) in dopamine D2 receptor-expressing medium spiny neurons (D2 MSNs) of mice regulate the excitability of these cells and control their striatopallidal globus pallidus external (GPe) projections. Lack of FTO in D2 MSNs translates into increased locomotor activity to novelty, associated with altered timing behavior, without impairing the ability to control actions or affecting reward-driven and conditioned behavior. Pharmacological manipulations of dopamine D1 receptor (D1R)- or D2R-dependent pathways in these animals reveal altered responses to D1- and D2-MSN-mediated control of motor output. These findings reveal a critical role for FTO to control D2 MSN excitability, their projections to the GPe, and behavioral responses to novelty.
  •  
50.
  • Samoudi, Ghazaleh, et al. (författare)
  • Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.
  • 2012
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS) may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of Parkinson's disease.
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