| 1. |
- Trägårdh, Karin, et al.
(författare)
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Risk Profiles of Female Perpetrators of Severe Violence
- 2019
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Ingår i: 13th Nordic Symposium on Forensic Psychiatry. August 20-22, Gothenburg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Female offenders without a severe mental disorder show more criminogenic factors than those with. Both groups are characterized by mental health problems. We need to further characterize female offenders. Background Offenders of lethal/severe violence are in a majority of cases male, about 90% (Falk et al., 2014), and research has to a considerable extent focused on male violent offenders. Although less is known about female violent offenders than male offenders, previous research has indicated significant differences between male and female offenders of lethal/severe violence (Trägårdh et al., 2016; Yourstone et al., 2008). Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation (RPU/FPI), these documents contains important information about this group. Purpose The aim of this ongoing study is to characterize female perpetrators of severe violent crimes, and to compare female perpetrators sentenced to forensic psychiatric compulsory care with those sentenced to correctional treatment. Method This is an exploratory and descriptive study with a cross-sectional design. All forensic evaluations (FPI) made in Sweden between 2000-2014 (from The National Board of Forensic Medicine/RMV), and the subsequent court verdicts, in cases where women had used lethal/severe violence (n≈180) where used as the basis for data collection in this study. The present preliminary analyses (2-tests and ANOVA) contains approx. 26% (n=47) of the total group. Group differences were investigated regarding: Mental health (FPI) Risk factors (HCR-20 and PCL-R) Victim relation (FPI) Criminal behavior (FPI) Results Female offenders with and without a Severe mental disorder (SMD) seems to differ in some respects. For female offenders with a SMD, the crime was more likely to have been conducted in a less criminal context (see Table). For female offenders without a SMD, the following characteristics were more frequently present: Victim gender – male Substance abuse + Under the influence of substance (offender and victim) Previous violence between victim and offender Previous registered criminality Also, several common features between the SMD and non-SMD group of female offenders were found. The majority of all female offenders had: Previous psychiatric contact and diagnoses Previously attempted suicide No previously registered criminality Conclusions Preliminary results of the female perpetrators who had underwent a FPI seems to identify both substantial differences and similarities between those with versus without a SMD, where those without show more criminogenic factors. Both groups were also characterized by a high amount of mental illness. Also, these results supports previous research that female and male offenders of severe violence differ in important ways. Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation, these results should be generalizable to this group as a whole in Sweden. Based on these results, a great need to further characterize female offenders of severe/lethal violence remain.
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| 2. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
- 2010
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Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have previously demonstrated that in young rats (12-20-day-old) a sustained long-term potentiation (LTP) can still be induced under conditions of protein synthesis inhibition. It was therefore suggested that sufficient and necessary proteins were already available at the induction time to accomplish LTP maintenance for several hours. Against this background, we have questioned whether hippocampal slices subjected to certain insult conditions might be more sensitive to protein synthesis inhibitors. High K+ concentration has previously been reported to cause an amnesic effect in vivo as well as increasing protein turnover in vitro. We have here employed a K+ insult model under conditions when protein synthesis was inhibited. Recordings were obtained from hippocampal slices for up to 9 h, with or without a cocktail of protein synthesis inhibitors, containing cycloheximide (60 µM) and anisomycin (25 µM). High potassium (50 mM) was transiently applied (5-15 min) shortly after inducing LTP in one of two separate pathways stimulated alternatively. Additionally, an NMDA-receptor antagonist AP5 was supplied after LTP induction to minimize effects related to depolarization-induced glutamate release. Following elimination of all responses for about 30 min, both test and control responses partly recovered. The degree of remaining LTP, defined as test/control ratio, was reduced in both groups of slices (NMDA-independent depotentiation) but was significantly smaller in the drug-treated ones. We are also running an insult model based on oxidative stress, applying hydrogen peroxide (4-5 mM) before or after LTP induction; however, the results are still insufficient for a final conclusion. The potency of cycloheximide, anisomycin or cocktail of the drugs was verified by measurement of incorporation of [3H]-leucine into trichloracetic acid (TCA) precipitable macromolecules. Cycloheximide, anisomycin or cocktail, at concentrations used here caused 95%, 97% and 95% blocking effect, respectively. Our data confirm the idea that sufficient and necessary constitutive proteins are available in the young hippocampus to maintain LTP under conditions of protein synthesis inhibition. They also reveal that LTP in slices subjected to certain insult conditions early after the induction is sensitive to protein synthesis inhibition, probably due to increase in constitutive proteins turnover.
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| 3. |
- Bauzá-Thorbrügge, Marco, et al.
(författare)
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NRF2 is essential for adaptative browning of white adipocytes.
- 2023
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Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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| 4. |
- Bergman, Penny, et al.
(författare)
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Age-related decline in senses and cognition : A Review
- 2021
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Ingår i: Senses and Sciences. - Rom : Eleven Senses Info. - 2284-2489. ; 8:2, s. 1264-1292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Age-related decline in the senses is well-known, with a decline in the sensitivity of all senses having been observed. Decline in the senses can be connected to different neurological disorders and cognitive function and may even be a possible predictor of death. Aim: The aim of this narrative review was to find and explore recent literature on the covariation between age-related decline in the different senses and co-existing effects on cognitive ability and quality of life. Results and Discussion: Six themes could be identified, these were: “Decline due to normal ageing?”, “Technical aids and solutions”, “Wellbeing”, “Memory training”, “Verbal exercises” and “Sensory training”. Large differences between the different senses were obtained. However, the senses showed similar patterns in the different themes. Conclusion: It could be concluded that there are many similarities concerning the connections between the decline in individual senses and cognition and memory. Measurements of wellbeing and quality of life are common in the evaluation of the senses, and all types of decline have an impact on activities in daily life.
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| 5. |
- Nilsson, Maria H., et al.
(författare)
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Psychometric properties of the general self-efficacy scale in Parkinson's disease
- 2015
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 132:2, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study aimed to investigate the psychometric properties of the General Self-Efficacy Scale (GSE) in people with Parkinson's disease (PD). More specifically, we investigated data completeness, scaling assumptions, targeting, reliability, and construct validity.MATERIALS AND METHODS: This study involves data available from two different projects that included people diagnosed with PD for at least 1 year, yielding two samples (1 and 2). The combined total sample (N = 346; 60% men) had a mean (SD) age and PD duration of 71 (8.9) and 9 years (6.3), respectively. Both samples received a self-administered survey by mail, which was administered twice in sample 2. Additional data (e.g., clinical assessments) were available for Sample 1.RESULTS: Total GSE scores were computable for 336 participants (97%). Corrected item-total correlations exceeded 0.4. Principal component analyses identified one component (the eigenvalue of the first component extracted was 6.9), explaining 69% of the total variance. Floor and ceiling effects were < 6%. Internal consistency (coefficient alpha) was 0.95. Analyses of test-retest reliability yielded (ICC) values from 0.69 to 0.80. The highest value refers to those (n = 47) with identical self-ratings of mobility (in the on condition) at both tests; the standard error of measurement was 3.1 points. Construct validity was further supported by correlations in accordance with a priori expectations.CONCLUSIONS: This study provides support for the validity and reliability of GSE scores in people with PD; the GSE can thus serve as a valuable outcome measurement in clinical practice and research.
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| 6. |
- Lindberg, Frida A., et al.
(författare)
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SLC38A10 knockout mice display a decreased body weight and an increased risk-taking behavior in the open field test
- 2022
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media S.A.. - 1662-5153. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- The solute carrier 38 family (SLC38) is a family of 11 members. The most commonsubstrate among these are alanine and glutamine, and members are present in a widerange of tissues with important functions for several biological processes, such as liverand brain function. Some of these transporters are better characterized than others and,in this paper, a behavioral characterization of SLC38A10−/− mice was carried out. Abattery of tests for general activity, emotionality, motor function, and spatial memorywere used. Among these tests, the elevated plus maze, Y-maze, marble burying, andchallenging beamwalk have not been tested on the SLC38A10−/− mice previously, whilethe open field and the rotarod tests have been performed by the International MousePhenotyping Consortium (IMPC). Unlike the results from IMPC, the results from this studyshowed that SLC38A10−/− mice spend less time in the wall zone in the open field testthan WT mice, implying that SLC38A10-deficient mice have an increased explorativebehavior, which suggests an important function of SLC38A10 in brain. The present studyalso confirmed IMPC’s data regarding rotarod performance and weight, showing thatSLC38A10−/− mice do not have an affected motor coordination impairment and havea lower body weight than both SLC38A10+/− and SLC38A10+/+ mice. These resultsimply that a complete deficiency of the SLC38A10 protein might affect body weighthomeostasis, but the underlying mechanisms needs to be studied further.
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| 7. |
- Lindberg, Frida A., et al.
(författare)
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SLC38A10 Deficiency in Mice Affects Plasma Levels of Threonine and Histidine in Males but Not in Females : A Preliminary Characterization Study of SLC38A10(-/-) Mice
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Solute carriers belong to the biggest group of transporters in the human genome, but more knowledge is needed to fully understand their function and possible role as therapeutic targets. SLC38A10, a poorly characterized solute carrier, is preliminary characterized here. By using a knockout mouse model, we studied the biological effects of SLC38A10 deficiency in vivo. We performed a transcriptomic analysis of the whole brain and found seven differentially expressed genes in SLC38A10-deficient mice (Gm48159, Nr4a1, Tuba1c, Lrrc56, mt-Tp, Hbb-bt and Snord116/9). By measuring amino acids in plasma, we found lower levels of threonine and histidine in knockout males, whereas no amino acid levels were affected in females, suggesting that SLC38A10(-/-) might affect sexes differently. Using RT-qPCR, we investigated the effect of SLC38A10 deficiency on mRNA expression of other SLC38 members, Mtor and Rps6kb1 in the brain, liver, lung, muscle, and kidney, but no differences were found. Relative telomere length measurement was also taken, as a marker for cellular age, but no differences were found between the genotypes. We conclude that SLC38A10 might be important for keeping amino acid homeostasis in plasma, at least in males, but no major effects were seen on transcriptomic expression or telomere length in the whole brain.
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| 8. |
- Rube, Tanja, et al.
(författare)
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Development of the Swedish anticholinergic burden scale (Swe-ABS).
- 2023
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Ingår i: BMC geriatrics. - 1471-2318. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research.A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process.The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group.Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.
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| 9. |
- Mottahedin, Amin
(författare)
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Developing brain and systemic inflammation: a "Toll-like" link with consequences
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The developing brain is vulnerable to external insults, and perinatal brain injury (PBI) is a major cause of life-long neurological syndromes such as cerebral palsy. Currently, no pharmaceutical intervention is available. Hypoxia/ischemia (HI), infections and inflammation are implicated in the pathogenesis of PBI. However, the crosstalk between these etiologies is not fully understood. Toll-like receptors (TLR) 3 and TLR2 are responsible for sensing viral and bacterial infections and initiating the inflammatory response. The aim of this thesis was to investigate the effect of systemic inflammation induced by activation of these TLRs on neonatal HI brain injury. We demonstrate that intraperitoneal administration of TLR3 and TLR2 ligands (PolyI:C and P3C, respectively) prior to HI increases the brain injury in neonatal mice. PolyI:C and P3C induced neuroinflammation and altered microglial phenotype as assessed by RT-qPCR, multiplex cytokine assay or flow cytometry. PolyI:C also upregulated the pro-apoptotic gene, Fasl, expression and reduced activation of pro-survival signaling molecule Akt. On the other hand, P3C suppressed mitochondrial respiration, a major mechanism of cellular energy production. P3C, unlike other TLR agonists, induced marked infiltration of leukocytes to the cerebral spinal fluid and brain of neonatal mice and rats. Confocal microscopy, Cre recombinase-mediated gene targeting and in vitro cell transmigra-tion assay revealed the choroid plexus as a site of leukocyte entry. RNA sequencing of the choroid plexus followed by transcriptome cluster analysis and Ingenuity Pathway Analysis revealed potential mechanisms of leukocyte infiltration, including a specific chemotaxis signature and cytoskeleton-related pathways. Finally, we show that N-acetylcysteine treatment inhibits TLR2-mediated leukocyte trafficking in vivo and in vitro. To conclude, this thesis describe a TLR-mediated link between systemic inflammation and developing brain with detrimental consequences on HI brain injury, suggesting potential novel therapeutic strategies.
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| 10. |
- Bergman, Penny, et al.
(författare)
-
Age-related decline in senses and cognition: A Review
- 2021
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Ingår i: Senses and Sciences. - : IVL Svenska Miljöinstitutet. - 2284-2489. ; 8:2, s. 1264-1292
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Age-related decline in the senses is well-known, with a decline in the sensitivity of all senses having been observed. Decline in the senses can be connected to different neurological disorders and cognitive function and may even be a possible predictor of death. Aim: The aim of this narrative review was to find and explore recent literature on the covariation between age-related decline in the different senses and co-existing effects on cognitive ability and quality of life. Results and Discussion: Six themes could be identified, these were: “Decline due to normal ageing?”, “Technical aids and solutions”, “Wellbeing”, “Memory training”, “Verbal exercises” and “Sensory training”. Large differences between the different senses were obtained. However, the senses showed similar patterns in the different themes. Conclusion: It could be concluded that there are many similarities concerning the connections between the decline in individual senses and cognition and memory. Measurements of wellbeing and quality of life are common in the evaluation of the senses, and all types of decline have an impact on activities in daily life.
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| 11. |
- Deshpande, J, et al.
(författare)
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Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death.
- 1992
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Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - 0014-4819. ; 88:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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| 12. |
- Izsak, Julia, et al.
(författare)
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Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABAA-receptor antagonist. Patch–clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.
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| 13. |
- Falk Erhag, Hanna, et al.
(författare)
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A Multidisciplinary Approach to Capability in Age and Ageing
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter by the editors summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
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| 14. |
- Lindberg, Frida A.
(författare)
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The Biological Importance of the Amino Acid Transporter SLC38A10 : Characterization of a Knockout Mouse
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The biggest group of transporters, the solute carriers (SLCs), has more than 400 members, and about 30% of these are still orphan. In order to decipher their biological function and possible role in disease, there is a need for characterization of these. Around 25% of SLCs are estimated to have amino acids as substrates, including transporters belonging to the SLC38 family. The SLC38 members are sometimes referred to their alternative name: sodium-coupled neutral amino acid transporters (SNATs). One of these transporters, SNAT10 (or SLC38A10), has been characterized as a bidirectional transporter of glutamate, glutamine, alanine and aspartate, as well as having an efflux of serine, and is ubiquitously expressed in the body. However, its biological importance is not yet understood. The aim with this thesis was to characterize a mouse model deficient in SNAT10 protein in order to find the biological importance of this transporter. In paper I, this is done by using a series of behavioral tests, including the open field test, elevated plus maze, rotarod and Y-maze, among others. The SNAT10 knockout mouse was found to have an increased risk-taking behavior, but no motor or spatial working memory impairments. Furthermore, the knockout mouse was found to have a decreased body weight. In paper II, an additional behavioral characterization was performed by using the multivariate concentric square field™ (MCSF) test. The MCSF test is an arena with different zones associated to different behavioral traits, which generates a behavioral profile depending on where the mouse spends its time. The result from this test implies that the SNAT10 deficient mouse has a lower explorative behavior than its wild type littermates. In paper III, gene expression was studied in whole brain and some genes related to cell cycle regulation and p53 expression were found to be differentially expressed in the knockout brain. Additional gene expression was studied in kidney, liver, lung and muscle, but no changes were found. Plasma levels of histidine and threonine were altered in males, but no altered amino acid levels were found in knockout females, suggesting a possible sex-specific effect. These studies together imply that SNAT10 might be involved in processes related to risk-taking and explorative behavior in the open field and MCSF tests. SNAT10 deficiency also affected amino acid levels in plasma, indicating a disrupted amino acid homeostasis.
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| 15. |
- Nyberg, Lars, et al.
(författare)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:52, s. 22682-22686
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 16. |
- Salami, Alireza, et al.
(författare)
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Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition
- 2012
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Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier. - 0925-4439 .- 1879-260X. ; 1822:3, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest. WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
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| 17. |
- Sukhovey, Yurij G., et al.
(författare)
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Functional Conjugation of the Different Regulatory Responses to the Stress Stimuli in Healthy Human Subjects
- 2016
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Ingår i: Open Journal of Applied Sciences. - : Scientific Research Publishing, Inc.. - 2165-3917 .- 2165-3925. ; 6, s. 489-500
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Tidskriftsartikel (refereegranskat)abstract
- Present article discusses the physiological mechanisms of the state employees adaptation duringactive training in temporary groups. It is suggested that adaptive mechanisms to adverse effectsmay be studied basing on the concept of functional isomorphism of the psychic and immune systems.Adaptive mechanisms were studied through the monitoring of the stress factors’ impact upon thelaw enforcement officers when training outside the places of permanent deployment. The specificpurpose of present study was to evaluate the physiological indicators of the psychic, immune andendocrine systems dynamics at different stages of adaptation of the live organism to a stressfulsituation, hoping to get better insight into possible relations between psychic and immune domains.Through monitoring of the dynamics of the endocrine and immune responses to the psychic stimuli,it was possible to correlate the stages of the stress onset to the phases of specific immune reactions.Strong correlations between the parameters characterizing activation of the psychic and immuneresponses support the hypothesis of the presence of “strong cooperation” between psychic andimmune domains. It supports earlier hypothesis that we are monitoring
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| 18. |
- Liu, Yawei, et al.
(författare)
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Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
- 2006
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 12:5, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
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| 19. |
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| 20. |
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| 21. |
- Mondal, Tanmoy, 1981, et al.
(författare)
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Sense-antisense lncRNA pair encoded by locus 6p22.3 determines neuroblastoma susceptibility via the USP36-CHD7-SOX9 regulatory axis
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.
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| 22. |
- Hogenkamp, Pleunie S, et al.
(författare)
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Sweet taste perception not altered after acute sleep deprivation in healthy young men.
- 2013
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Ingår i: Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine. - : Springer Science and Business Media LLC. - 1432-9123 .- 1439-054X. ; 17:2, s. 111-114
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that acutely sleep-deprived participants would rate ascending concentrations of sucrose as more intense and pleasant, than they would do after one night of normal sleep. Such a finding would offer a potential mechanism through which acute sleep loss could promote overeating in humans.
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| 23. |
- Bhandage, Amol K., 1988-
(författare)
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Glutamate and GABA signalling components in the human brain and in immune cells
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glutamate and γ-aminobutyric acid (GABA) are the principal excitatory and inhibitory neurotransmitters in the central nervous system (CNS). They both can activate their ionotropic and metabotropic receptors. Glutamate activates ionotropic glutamate receptors (iGlu - AMPA, kainate and NMDA receptors) and GABA activates GABA-A receptors which are modulated by many types of drugs and substances including alcohol. Using real time quantitative polymerase chain reaction, I have shown that iGlu and/or GABA-A receptor subunits were expressed in the hippocampus dentate gyrus (HDG), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), central amygdala (CeA), caudate and putamen of the human brain and their expression was altered by chronic excessive alcohol consumption. It indicates that excitatory and inhibitory neurotransmission may have been altered in the brain of human alcoholics. It is possible that changes in one type of neurotransmitter system may drive changes in another. These brain regions also play a role in brain reward system. Any changes in them may lead to changes in the normal brain functions.Apart from the CNS, glutamate and GABA are also present in the blood and can be synthesised by pancreatic islet cells and immune cells. They may act as immunomodulators of circulating immune cells and can affect immune function through glutamate and GABA receptors. I found that T cells from human, rat and mouse lymph nodes expressed the mRNAs and proteins for specific GABA-A receptor subunits. GABA-evoked transient and tonic currents recorded using the patch clamp technique demonstrate the functional GABA-A channel in T cells. Furthermore, the mRNAs for specific iGlu, GABA-A and GABA-B receptor subunits and chloride cotransporters were detected in peripheral blood mononuclear cells (PBMCs) from men, non-pregnant women, healthy and depressed pregnant women. The results indicate that the expression of iGlu, GABA-A and GABA-B receptors is related to gender, pregnancy and mental health and support the notion that glutamate and GABA receptors may modulate immune function. Intra- and interspecies variability exists in the expression and it is further influenced by physiological conditions.
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| 24. |
- Giddaluru, Sudheer, et al.
(författare)
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Genetics of structural connectivity and information processing in the brain
- 2016
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Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 221:9, s. 4643-4661
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
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| 25. |
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