SwePub - search: WFRF:(Wasling Pontus 1970)

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1.	Kalm, Marie, 1981, et al. (author) Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation. 2014 In: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 89:3, s. 607-614 Journal article (peer-reviewed)abstract Toexamine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β-related processes could characterize the neurochemical response to cranial radiation.
2.	Lundblad, Linda, et al. (author) Tactile direction discrimination in humans after stroke 2020 In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:2 Journal article (peer-reviewed)abstract Sensing movements across the skin surface is a complex task for the tactile sensory system, relying on sophisticated cortical processing. Functional MRI has shown that judgements of the direction of tactile stimuli moving across the skin are processed in distributed cortical areas in healthy humans. To further study which brain areas are important for tactile direction discrimination, we performed a lesion study, examining a group of patients with first-time stroke. We measured tactile direction discrimination in 44 patients, bilaterally on the dorsum of the hands and feet, within 2 weeks (acute), and again in 28 patients 3 months after stroke. The 3-month follow-up also included a structural MRI scan for lesion delineation. Fifty-nine healthy participants were examined for normative direction discrimination values. We found abnormal tactile direction discrimination in 29/44 patients in the acute phase, and in 21/28 3 months after stroke. Lesions that included the opercular parietal area 1 of the secondary somatosensory cortex, the dorsolateral prefrontal cortex or the insular cortex were always associated with abnormal tactile direction discrimination, consistent with previous functional MRI results. Abnormal tactile direction discrimination was also present with lesions including white matter and subcortical regions. We have thus delineated cortical, subcortical and white matter areas important for tactile direction discrimination function. The findings also suggest that tactile dysfunction is common following stroke.
3.	Wasling, Helena Backlund, 1972, et al. (author) Quality of life and procrastination in post-H1N1 narcolepsy, sporadic narcolepsy and idiopathic hypersomnia, a Swedish cross-sectional study 2020 In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 76, s. 104-112 Journal article (peer-reviewed)abstract Objective/Background: A cross-sectional study of health-related quality of life (HRQoL), procrastination and the relation to sleepiness, depression and fatigue in post-H1N1 narcolepsy type 1 (NT1), sporadic NT1 and idiopathic hypersomnia (IH). Patients/Methods: Participants with NT1 and IH were enrolled from the Department of Neurology, Sahlgrenska University Hospital in Gothenburg (Sweden). All participants completed questionnaires about medication, employment, studies, transfer income, sleepiness, HRQoL, depression, fatigue and three questionnaires for procrastination. Results: Post-H1N1, sporadic NT1 and IH all scored higher than healthy controls on Epworth Sleepiness Scale (ESS), Patient Health Questionnaire (PHQ-9) and Fatigue Severity Scale (FSS), whereas EQ-5D-5L index and VAS was lower than for healthy individuals, but with no difference between groups. Post-H1N1 NT1 had a larger proportion of participants prescribed with sodium oxybate (44% vs. 9%, p = 0.003) and dexamphetamine (62% vs. 17%, p = 0.03) compared to sporadic NT1. The latter also in significantly higher doses than in sporadic NT1 (46 +/- 12 vs. 25 +/- 10 and 47.5 +/- 21 mg, p < 0.0001). Post-H1N1 NT1 also had significantly higher scores on Pure Procrastination Scale (PPS), Irrational Procrastination Scale (IPS) and Susceptibility to Temptation Scale (STS), indicating a higher degree of procrastination. Multivariate analysis showed that depression, and to some extent fatigue, were predictors in NT1 for both HRQoL and procrastination. Conclusions: The results show that health-related quality of life is impaired and tendency to procrastinate is higher in patients suffering from NT1 and both attributes can in part be explained by depressive symptoms. These findings highlight the impact of symptoms other than sleep and wakefulness regulation in patients with NT1. (C) 2020 Elsevier B.V. All rights reserved.
4.	Asp, Amanda, et al. (author) Impaired procedural memory in narcolepsy type 1 2022 In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 146:2, s. 186-193 Journal article (peer-reviewed)abstract Objectives Sleep enhances the consolidation of memories. Here, we investigated whether sleep-dependent memory consolidation differs between healthy subjects and narcolepsy type 1 (NT1) patients. Material and Methods We recruited 18 patients with NT1 and 24 healthy controls. The consolidation of spatial (declarative memory; 2-dimensional object location) and procedural (non-declarative memory; finger sequence tapping) memories was examined across one night of at-home sleep. Sleep was measured by an ambulatory sleep recording device. Results The overnight gain in the number of correctly recalled sequences in the finger-tapping test was smaller for NT1 patients than healthy subjects (+8.1% vs. +23.8% from pre-sleep learning to post-sleep recall, p = .035). No significant group differences were found for the overnight consolidation of spatial memory. Compared to healthy subjects, the sleep of NT1 patients was significantly more fragmented and shallow. However, no significant correlations were found between sleep parameters and overnight performance changes on the memory tests in the whole group. Conclusion The sleep-dependent consolidation of procedural but not spatial memories may be impaired among patients with NT1. Therefore, future studies are warranted to examine whether sleep improvement, for example, using sodium oxybate, can aid the sleep-dependent formation of procedural memories among NT1 patients.
5.	Björefeldt, Andreas, 1982, et al. (author) Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice. 2015 In: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 593:1, s. 231-43 Journal article (peer-reviewed)abstract The cerebrospinal fluid contains numerous neuromodulators at ambient levels but whether, and how, they affect the activity of central neurons is unknown. This study provides experimental evidence that human cerebrospinal fluid (hCSF) increases the excitability of hippocampal and neocortical pyramidal neurons. Hippocampal CA1 pyramidal neurons in hCSF displayed lowered firing thresholds, depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The excitability-increasing effect of hCSF on CA1 pyramidal neurons was entirely occluded by intracellular application of GTPγS, suggesting that neuromodulatory effects were mediated by G-protein coupled receptors. These results indicate that the CSF promotes spontaneous excitatory neuronal activity, and may help to explain observed differences in the activity of pyramidal neurons recorded in vivo and in vitro.
6.	Björefeldt, Andreas, 1982, et al. (author) Neuromodulation of fast-spiking and non-fast-spiking hippocampal CA1 interneurons by human cerebrospinal fluid. 2016 In: The Journal of physiology. - 1469-7793. ; 594:4, s. 937-52 Journal article (peer-reviewed)abstract GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks. Their function in vivo is likely to be tuned by neuromodulatory substances in brain extracellular fluid. However, in vitro investigations of GABAergic interneuron function do not account for such effects, as neurons are kept in artificial extracellular fluid. To examine the neuromodulatory influence of brain extracellular fluid on GABAergic activity, we recorded from fast-spiking and non-fast-spiking CA1 interneurons, as well as from pyramidal cells, in the presence of human cerebrospinal fluid (hCSF), using a matched artificial cerebrospinal (aCSF) fluid as control. We found that hCSF increased the frequency of spontaneous firing more than twofold in the two groups of interneurons, and more than fourfold in CA1 pyramidal cells. hCSF did not affect the resting membrane potential of CA1 interneurons but caused depolarization in pyramidal cells. The increased excitability of interneurons and pyramidal cells was accompanied by reductions in afterhyperpolarization amplitudes and a left-shift in the frequency-current relationships. Our results suggest that ambient concentrations of neuromodulators in the brain extracellular fluid powerfully influence the excitability of neuronal networks. This article is protected by copyright. All rights reserved.
7.	Bolin, Kristian, et al. (author) The cost utility of pitolisant as narcolepsy treatment 2020 In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:4, s. 301-310 Journal article (peer-reviewed)abstract Objectives The cost-effectiveness of available pharmacological treatments for narcolepsy is largely
8.	Bolin, Kristian, et al. (author) The cost-utility of sodium oxybate as narcolepsy treatment 2017 In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 136:6, s. 715-720 Journal article (peer-reviewed)abstract Aims and ObjectivesBased on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. Materials and MethodsCalculations were performed using a Markov model with a 10-year time horizon. The study population consisted of adult patients treated for narcolepsy with cataplexy. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. ResultsThe cost per additional quality-adjusted life year was estimated at SEK 563,481. The cost-effectiveness measure was demonstrated to be particularly sensitive to the duration of the relative quality-of-life improvements accruing to patients treated with sodium oxybate. ConclusionsThe estimated cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio as potentially beneficial effects on productivity of treatment with sodium oxybate were not included (due to lack of data).
9.	Bornstein, Axel, et al. (author) Actigraphy measurement of physical activity and energy expenditure in narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia: A Sensewear Armband study 2021 In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:2 Journal article (peer-reviewed)abstract The cause of obesity in narcolepsy type 1 (NT1) patients is not fully understood. The present study investigated if a reduced physical activity could explain weight gain in NT1. Seventy-nine patients were included in this retrospective study and divided into an NT1 group (n = 56) and a non-NT1 group (n = 23), including NT2 and idiopathic hypersomnia (IH). Accelerometry-derived measures of physical activity, total energy expenditure and skin temperature were collected from patients during seven consecutive days without medication. In addition, results from multiple sleep latency tests and the Epworth Sleepiness Scale questionnaire, body weight, height and CSF orexin/hypocretin were acquired. Three measurements of physical activity, including metabolic equivalent of task (MET), the average time of physical activity and step count, were compared without differences between groups. Neither could we find a significant difference in total energy expenditure or skin temperature. Thus, by analysing accelerometric data, we could not find any differences in the amount of physical activity or total energy expenditure explaining overweight in NT1.
10.	Fernström, Erik, et al. (author) Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy 2018 In: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 284:2, s. 211-225 Journal article (peer-reviewed)abstract Background Advances in the treatment of brain tumours have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers are of great clinical interest. Objective Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signalling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain. Methods Patients with small-cell lung cancer (SCLC) eligible for prophylactic cranial irradiation (PCI) were asked to participate in the study. PCI was prescribed either as 2 Gy/fraction to a total dose of 30 Gy (limited disease) or 4 Gy/fraction to 20 Gy (extensive disease). CSF was collected by lumbar puncture at baseline, 3 months and 1 year following PCI. Protein concentrations were measured using immunobased assays or mass spectrometry. Results The inflammatory markers IL-15, IL-16 and MCP-1/CCL2 were elevated in CSF 3 months following PCI compared to baseline. The plasticity marker GAP-43 was elevated 3 months following PCI, and the same trend was seen for SNAP-25, but not for SYT1. The investigated ECM proteins, brevican and neurocan, showed a decline following PCI. There was a strong correlation between the progressive decline of soluble APP and brevican levels. Conclusion To our knowledge, this is the first time ECM-related proteins have been shown to be affected by cranial radiotherapy in patients with cancer. These findings may help us to get a better understanding of the mechanisms behind side effects following radiotherapy.
11.	Forsberg, My, et al. (author) Ion concentrations in cerebrospinal fluid in wakefulness, sleep and sleep deprivation in healthy humans 2022 In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:3 Journal article (peer-reviewed)abstract Sleep is controlled by a circadian rhythmicity, via a reduction of arousal-promoting neuromodulatory activity, and by accumulation of somnogenic factors in the interstitial fluid of the brain. Recent experiments in mice suggest that a reduced neuronal excitability caused by a reduced concentration of potassium in the brain, concomitant with an increased concentration of calcium and magnesium, constitutes an important mediator of sleep. In the present study, we examined whether such changes in ion concentrations could be detected in the cerebrospinal fluid of healthy humans. Each subject underwent cerebrospinal fluid collection at three occasions in a randomized order: at 15:00 hours–17:00 hours during waking, at 06:00 hours–07:00 hours immediately following 1 night of sleep, and at 06:00 hours–07:00 hours following 1 night of sleep deprivation. When compared with wakefulness, both sleep and sleep deprivation produced the same effect of a small (0.1mm, about 3%), but robust and highly significant, reduction in potassium concentration. Calcium and magnesium concentrations were unchanged. Our results support a circadian modulation of neuronal excitability in the brain mediated via changes of the interstitial potassium concentration.
12.	Forsberg, My, et al. (author) Ionized calcium in human cerebrospinal fluid and its influence on intrinsic and synaptic excitability of hippocampal pyramidal neurons in the rat. 2019 In: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 149:4, s. 452-470 Journal article (peer-reviewed)abstract It is well-known that the extracellular concentration of calcium affects neuronal excitability and synaptic transmission. Less is known about the physiological concentration of extracellular calcium in the brain. In electrophysiological brain slice experiments, the artificial cerebrospinal fluid traditionally contains relatively high concentrations of calcium (2-4 mM) to support synaptic transmission and suppress neuronal excitability. Using an ion-selective electrode, we determined the fraction of ionized calcium in healthy human cerebrospinal fluid to 1.0mM of a total concentration of 1.2 mM (86%). Using patch-clamp and extracellular recordings in the CA1 region in acute slices of rat hippocampus, we then compared the effects of this physiological concentration of calcium with the commonly used 2 mM on neuronal excitability, synaptic transmission, and long-term potentiation (LTP) to examine the magnitude of changes in this range of extracellular calcium. Increasing the total extracellular calcium concentration from 1.2 to 2 mM decreased spontaneous action potential firing, induced a depolarization of the threshold, and increased the rate of both de- and repolarization of the action potential. Evoked synaptic transmission was approximately doubled, with a balanced effect between inhibition and excitation. In 1.2mM calcium high-frequency stimulation did not result in any LTP, whereas a prominent LTP was observed at 2 or 4 mM calcium. Surprisingly, this inability to induce LTP persisted during blockade of GABAergic inhibition. In conclusion, an increase from the physiological 1.2 mM to 2 mM calcium in the artificial cerebrospinal fluid has striking effects on neuronal excitability, synaptic transmission, and the induction of LTP.
13.	Johansson, Kalle, et al. (author) Cerebrospinal fluid amyloid precursor protein as a potential biomarker of fatigue in multiple sclerosis: A pilot study 2022 In: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348. ; 63 Journal article (peer-reviewed)abstract Background: Fatigue is the major cause of disability in MS. Fatigue has been suggested to be primary, part of the neurological disease; it can also be secondary to other diseases outside the CNS or exist as a separate comorbidity. The only forms of measurement currently available are through subjective standardized questionnaires, which are not able to identify primary MS-related fatigue. Therefore, there is a need for objective biomarkers of fatigue in MS. This study explored the viability of 17 possible biomarkers of primary fatigue in MS. Our chosen biomarker panel represents the function and health of different parts of the CNS. Methods: We evaluated 31 MS patients and 17 healthy controls using the Fatigue Severity Scale (FSS) and Insomnia Severity Index (ISI). We assessed clinical parameters and collected CSF from all participants to analyze 17 biomarkers, some of which in multiple targeted sequences, reflecting structural and functional changes in the brain. Based on FSS scores, MS was divided into MS-Fatigue (MS-F, FSS >= 4) and MS-NoFatigue (MS-NoF, FSS < 4). Results: MS-F had significantly lower levels of amyloid precursor protein (APP) peptides than MS-NoF (p = 0.005, p = 0.011). The only biomarker correlating with FSS in any group was APP in MS (r = -0.47, -0.52; p = 0.007, 0.002). APP did not correlate with any clinical parameter in MS but correlated with multiple markers. In MS, FSS correlated with the ISI and months since diagnosis. Conclusion: Although the mechanisms remain unknown, altered APP metabolism in MS seems to be associated with fatigue. APP should be evaluated as a biomarker of the role of structural MS pathology in the development of fatigue in individual MS patients.
14.	Johansson, Kalle, et al. (author) Fatigue, insomnia and daytime sleepiness in multiple sclerosis versus narcolepsy 2021 In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 144:5, s. 566-575 Journal article (peer-reviewed)abstract Objectives In multiple sclerosis (MS), fatigue is the most prevalent cause of impaired ability to work. In narcolepsy, daytime sleepiness is the main symptom but some studies indicate fatigue being present. We aimed to assess fatigue and associated features in patients with MS or narcolepsy and healthy controls and to assess whether clinical parameters separate fatigued (MS-F) and non-fatigued MS patients (MS-NoF). Materials & Methods In this non-interventional cross-sectional study, we recruited 34 MS patients, 15 narcolepsy type 1 patients and 17 healthy controls. An interviewer administered the Fatigue Severity Scale (FSS), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale, the Patient Health Questionnaire-9 and the Saltin-Grimby Physical Activity Level Scale. Information about clinical parameters and current treatments was collected. Results In its fatigue profile, MS-F resembled the narcolepsy group rather than MS-NoF, which resembled the healthy control group. ISI alone was significantly associated with FSS, and only in MS-NoF and healthy controls; in MS-F and the narcolepsy group, no variable was associated with FSS. Months since diagnosis was the only clinical variable significantly separating MS-F from MS-NoF. In MS, disease duration correlated with fatigue. No clinical variables correlated with fatigue in the narcolepsy group. Conclusions Fatigued MS patients resemble narcolepsy patients more than they resemble non-fatigued MS patients, who resemble healthy controls. Insomnia is the main factor associated with fatigue in MS, while disease duration is the only clinical variable separating fatigued and non-fatigued MS patients. In fatigued patients, variance in fatigue cannot be explained by insomnia, daytime sleepiness, depression or level of exercise.
15.	Kim, Malin, et al. (author) Antisecretory factor modulates GABAergic transmission in the rat hippocampus. 2005 In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 129:1-3, s. 109-18 Journal article (peer-reviewed)abstract Antisecretory Factor (AF) is a protein that has been implicated in the suppression of intestinal hypersecretion and inflammation. Intestinal secretion and inflammation are partly under local and central neural control raising the possibility that AF might exert its action by modulating neural signaling. In the present study we have investigated whether AF can modulate central synaptic transmission. Evoked glutamatergic and GABAergic synaptic transmissions were investigated using extracellular recordings in the CA1 region of hippocampal slices from adult rats. AF (0.5 microg/ml) suppressed GABA(A)-mediated synaptic transmission by about 40% while having no effect on glutamatergic transmission. Per oral administration of cholera toxin as well as feeding of rats with a diet containing hydrothermally processed cereals, known to upregulate endogenous AF plasma activity, mimicked the effect of exogenously administered AF on hippocampal GABAergic transmission. Our results identify AF as a neuromodulator and further raise the possibility that the hippocampus and AF are involved in a gut-brain loop controlling intestinal secretion and inflammation.
16.	Pelletier, F., et al. (author) Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C 2021 In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2 Journal article (peer-reviewed)abstract Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
17.	Perez-Alcazar, Marta, et al. (author) Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3. 2014 In: Experimental neurology. - : Elsevier BV. - 1090-2430 .- 0014-4886. ; 253C, s. 154-164 Journal article (peer-reviewed)abstract Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured CNS. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.
18.	Perez-Alcazar, Marta, et al. (author) Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro 2016 In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10 Journal article (peer-reviewed)abstract For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.
19.	Strandberg, Joakim, 1978, et al. (author) Modulation of low-frequency-induced synaptic depression in the developing CA3-CA1 hippocampal synapses by NMDA and metabotropic glutamate receptor activation. 2009 In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 101:5, s. 2252-62 Journal article (peer-reviewed)abstract Brief test-pulse stimulation (0.2-0.05 Hz) of naïve (previously nonstimulated) developing hippocampal CA3-CA1 synapses leads to a substantial synaptic depression, explained by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silencing. Using field recordings in hippocampal slices from P8 to P12 rats, we examined this depression of naïve synapses using more prolonged test-pulse stimulation as well as low-frequency (1 Hz) stimulation (LFS). We found that 900 stimuli produced depression during stimulation to approximately 40% of the naïve level independent of whether test-pulse stimulation or LFS was used. This result was also observed during combined blockade of N-methyl-d-aspartate/metabotropic glutamate receptors (NMDAR/mGluRs) although the depression was smaller (to approximately 55% of naïve level). Using separate blockade of either NMDARs or mGluRs, we found that this impairment of the depression resulted from the NMDAR, and not from the mGluR, blockade. In fact, during NMDAR blockade alone, depression was smaller even than that observed during combined blockade. We also found that mGluR blockade alone facilitated the LFS-induced depression. In conclusion, test-pulse stimulation produced as much depression as LFS when applied to naïve synapses even when allowing for NMDAR and mGluR activation. Our results seem in line with the notion that NMDARs and mGluRs may exert a bidirectional control on AMPA receptor recruitment to synapses.
20.	Wasling, Pontus, 1970, et al. (author) AMPA receptor activation causes silencing of AMPA receptor-mediated synaptic transmission in the developing hippocampus 2012 In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4 Journal article (peer-reviewed)abstract Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses.
21.	Wasling, Pontus, 1970, et al. (author) CSF orexin-A levels after rituximab treatment in recent onset narcolepsy type 1 2019 In: Neurology, neuroimmunology & neuroinflammation. - 2332-7812. ; 6:6 Journal article (peer-reviewed)
22.	Wasling, Pontus, 1970, et al. (author) Developmental changes in release properties of the CA3-CA1 glutamate synapse in rat hippocampus. 2004 In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:5, s. 2714-24 Journal article (peer-reviewed)abstract Developmental changes in release probability (Pr) and paired-pulse plasticity at CA3-CA1 glutamate synapses in hippocampal slices of neonatal rats were examined using field excitatory postsynaptic potential (EPSP) recordings. Paired-pulse facilitation (PPF) at these synapses was, on average, absent in the first postnatal week but emerged and became successively larger during the second postnatal week. This developmental increase in PPF was associated with a reduction in Pr, as indicated by the slower progressive block of the N-methyl-D-aspartate (NMDA) EPSP by the noncompetitive NMDA receptor antagonist MK-801. This developmental reduction in Pr was not homogenous among the synapses. As shown by the MK-801 analysis, the Pr heterogeneity observed among adult CA3-CA1 synapses is present already during the first postnatal week, and the developmental Pr reduction was found to be largely selective for synapses with higher Pr values, leaving Pr of the vast majority of the synapses essentially unaffected. A reduction in Pves, the release probability of the individual vesicle, possibly caused by reduction in Ca2+ influx, seems to explain the reduction in Pr. In vivo injection of tetanus toxin at the end of the first postnatal week did not prevent the increase in PPF, indicating that this developmental change in release is not critically dependent on normal neural activity during the second postnatal week.
23.	Xiao, Min-Yi, 1964, et al. (author) Creation of AMPA-silent synapses in the neonatal hippocampus. 2004 In: Nature neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 7:3, s. 236-43 Journal article (peer-reviewed)abstract In the developing brain, many glutamate synapses have been found to transmit only NMDA receptor-mediated signaling, that is, they are AMPA-silent. This result has been taken to suggest that glutamate synapses are initially AMPA-silent when they are formed, and that AMPA signaling is acquired through activity-dependent synaptic plasticity. The present study on CA3-CA1 synapses in the hippocampus of the neonatal rat suggests that AMPA-silent synapses are created through a form of activity-dependent silencing of AMPA signaling. We found that AMPA signaling, but not NMDA signaling, could be very rapidly silenced by presynaptic electrical stimulation at frequencies commonly used to probe synaptic function (0.05-1 Hz). Although this AMPA silencing required a rise in postsynaptic Ca(2+), it did not require activation of NMDA receptors, metabotropic glutamate receptors or voltage-gated calcium channels. The AMPA silencing, possibly explained by a removal of postsynaptic AMPA receptors, could subsequently be reversed by paired presynaptic and postsynaptic activity.

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