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Synaptive Medical

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https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#1
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29785777/paradoxical-effect-of-baclofen-on-social-behavior-in-the-fragile-x-syndrome-mouse-model
#2
Shimriet Zeidler, Andreea S Pop, Israa A Jaafar, Helen de Boer, Ronald A M Buijsen, Celine E F de Esch, Ingeborg Nieuwenhuizen-Bakker, Renate K Hukema, Rob Willemsen
INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse...
April 26, 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29768974/brain-phospholipid-precursors-administered-post-injury-reduce-tissue-damage-and-improve-neurological-outcome-in-experimental-traumatic-brain-injury
#3
Orli Thau-Zuchman, Rita Noutel Gomes, Simon Christopher Dyall, Meirion Davis, John V Priestley, Martine Groenendijk, Martijn DE Wilde, Jordi Lopez-Tremoleda, Adina T Michael-Titus
Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use...
May 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29753198/prefrontal-alterations-in-gabaergic-and-glutamatergic-gene-expression-in-relation-to-depression-and-suicide
#4
J Zhao, R W H Verwer, S-F Gao, X-R Qi, P J Lucassen, H W Kessels, D F Swaab
People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to depression per se. We used quantitative PCR to determine mRNA levels of 32 genes encoding for proteins directly involved in glutamatergic or GABAergic synaptic transmission in postmortem samples of the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC)...
April 30, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29737971/differential-electrical-responses-in-retinal-ganglion-cell-subtypes-effects-of-synaptic-blockade-and-stimulating-electrode-location
#5
Chih Yu Yang, David Tsai, Tianruo Guo, Socrates Dokos, Gregg J Suaning, John W Morley, Nigel H Lovell
OBJECTIVE: Visual prostheses have shown promising results in restoring visual perception to blind patients. The ability to differentially activate retinal ganglion cell (RGC) subtypes could further improve the efficacy of these medical devices. APPROACH: Using whole-cell patch clamp, we investigated membrane potential differences between ON and OFF RGCs in the mouse retina when their synaptic inputs were blocked by synaptic blockers, and examined the differences in stimulation thresholds under such conditions...
May 8, 2018: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29686940/complete-resolution-of-symptoms-of-primary-orthostatic-tremor-with-perampanel
#6
María Ruiz-Julián, Jorge Luís Orozco, Alexandre Gironell
Background: Primary orthostatic tremor (POT) is an infrequent disorder whose physiopathology is unknown. Current medication is largely ineffective or only offers mild benefits. Case Report: A 75-year-old female with refractory POT treated with 4 mg/day of perampanel achieved complete symptom resolution. Owing to adverse effects, the patient reduced intake to 2 mg/day, but even at this lower dose the benefit was maintained. Discussion: We report the complete resolution of POT symptoms using low doses of perampanel, an antiepileptic drug that blocks glutamate-mediated post-synaptic excitation...
2018: Tremor and Other Hyperkinetic Movements
https://www.readbyqxmd.com/read/29685421/altered-short-term-neural-plasticity-related-to-schizotypal-traits-evidence-from-visual-adaptation
#7
Katharine N Thakkar, Anna Antinori, Olivia L Carter, Jan W Brascamp
Abnormalities in synaptic plasticity are argued to underlie the neural dysconnectivity observed in schizophrenia. One way to measure synaptic plasticity is through sensory adaptation, whereby sensory neurons exhibit reduced sensitivity after sustained stimulus exposure. Evidence for decreased adaptation in individuals with schizophrenia is currently inconclusive, possibly due to heterogeneity in clinical and medication status across samples. Here we circumvent these confounds by examining whether altered adaptation is represented sub-clinically in the general population...
April 20, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29651456/systematic-reconstruction-of-autism-biology-from-massive-genetic-mutation-profiles
#8
Weijun Luo, Chaolin Zhang, Yong-Hui Jiang, Cory R Brouwer
Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module)...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29649119/crystal-structure-of-botulinum-neurotoxin-a2-in-complex-with-the-human-protein-receptor-sv2c-reveals-plasticity-in-receptor-binding
#9
Robert Gustafsson, Sicai Zhang, Geoffrey Masuyer, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We here present a high resolution (2...
April 12, 2018: Toxins
https://www.readbyqxmd.com/read/29644157/persistent-bradycardia-with-the-long-term-use-of-phenytoin-and-oxycodone-first-case-report
#10
Intekhab Askari Syed, Aaron R Kuzel, Muhammad Uzair Lodhi, Waliul Chowdhury, Umar Rahim, Mustafa Rahim
Phenytoin is a medication that is used primarily in the treatment of epilepsy as well as generalized tonic-clonic seizures and status epilepticus. Phenytoin is also considered a class IB antiarrhythmic medication by shortening the duration of the action potential and increasing myocardial conduction. The neurologic adverse effects of phenytoin are well-documented and include altered mental status, ataxia, and nystagmus. Some adverse cardiac manifestations have also been reported, including arrhythmias, hypotension, and respiratory arrest...
February 8, 2018: Curēus
https://www.readbyqxmd.com/read/29625107/cephalosporin-antibiotics-are-weak-blockers-of-gabaa-receptor-mediated-synaptic-transmission-in-rat-brain-slices
#11
Dmitry V Amakhin, Elena B Soboleva, Aleksey V Zaitsev
Cephalosporins are beta-lactam antibiotics that are extensively used in medical practice and are reported to cause epileptic seizures in some patients. The primary cause of cephalosporin-induced convulsions is believed to be their ability to block GABAa receptors. However, direct evidence for the involvement of this mechanism has not yet been provided. The present study aims to investigate the ability of two cephalosporins - cefepime and ceftriaxone - to block inhibitory synaptic transmission in entorhinal cortex slices of rats...
April 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29622647/crmp2-binding-compound-edonerpic-maleate-accelerates-motor-function-recovery-from-brain-damage
#12
Hiroki Abe, Susumu Jitsuki, Waki Nakajima, Yumi Murata, Aoi Jitsuki-Takahashi, Yuki Katsuno, Hirobumi Tada, Akane Sano, Kumiko Suyama, Nobuyuki Mochizuki, Takashi Komori, Hitoshi Masuyama, Tomohiro Okuda, Yoshio Goshima, Noriyuki Higo, Takuya Takahashi
Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization...
April 6, 2018: Science
https://www.readbyqxmd.com/read/29562539/a-novel-therapeutic-approach-to-treat-alzheimer-s-disease-by-neurotrophic-support-during-the-period-of-synaptic-compensation
#13
Narjes Baazaoui, Khalid Iqbal
Alzheimer's disease (AD), at present, is considered an incurable disease and a major dilemma with no drug to stop or slow down its progression. Drugs that are currently available in the market are able to only transiently improve the clinical symptoms. The repeated failures in developing an effective drug has led to the suggestion that the medical intervention was probably too late to be effective since the pathology starts many years before the appearance of the clinical symptoms. Probably, at the time of the appearance of clinical symptoms the brain has undergone major neuronal and synaptic loss...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29559905/molecular-mechanisms-for-herpes-simplex-virus-type-1-pathogenesis-in-alzheimer-s-disease
#14
REVIEW
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29540745/structural-characterisation-of-the-catalytic-domain-of-botulinum-neurotoxin-x-high-activity-and-unique-substrate-specificity
#15
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29522760/stress-evoking-emotional-stimuli-exaggerate-deficits-in-motor-function-in-parkinson-s-disease
#16
R L Blakemore, M R MacAskill', R Shoorangiz, T J Anderson
Recent animal studies have shown that stress can profoundly affect motor behaviour and worsen motor deficits associated with Parkinson's disease (PD) by acting on the dopaminergic system, possibly due to stress-associated emotional changes. However, systematic investigation of the influence of acute emotional stressors on motor function in PD is scarce. Here we examined the effect of repeated exposure to negative emotional stimuli on grip-force control in PD. Eighteen patients with idiopathic PD (tested off-medication) and 18 healthy controls produced an isometric precision grip contraction at 15% of maximum force while viewing a series of unpleasant, pleasant, or neutral emotional images (blocked presentation; without visual feedback of force output)...
April 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29520222/immediate-early-genes-anchor-a-biological-pathway-of-proteins-required-for-memory-formation-long-term-depression-and-risk-for-schizophrenia
#17
Ketan K Marballi, Amelia L Gallitano
While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29476014/positive-allosteric-modulation-as-a-potential-therapeutic-strategy-in-anti-nmda-receptor-encephalitis
#18
Natasha Warikoo, Samuel J Brunwasser, Ann Benz, Hong-Jin Shu, Steven M Paul, Michael Lewis, James Doherty, Michael Quirk, Laura Piccio, Charles F Zorumski, Gregory S Day, Steven Mennerick
N -methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29471055/brain-insulin-signalling-glucose-metabolism-and-females-reproductive-aging-a-dangerous-triad-in-alzheimer-s-disease
#19
REVIEW
A I Duarte, M S Santos, C R Oliveira, P I Moreira
Alzheimer's disease (AD) constitutes a major socioeconomic challenge due to its disabling features and the rise in prevalence (especially among (peri)menopausal women and type 2 diabetes patients). The precise etiopathogenesis of AD remains poorly understood. Importantly, its neurodegenerative perspective has been challenged towards a more "systemic" view. Amyloid-β (Aβ) and hyperphosphorylated Tau protein (P-Tau) (the main AD neuropathological features) affect and are affected by peripheral and brain insulin signalling dysfunction, leading to glucose dysmetabolism, synaptic loss and AD-related cognitive deficits...
February 20, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29434537/how-can-a-ketogenic-diet-improve-motor-function
#20
REVIEW
Charlotte Veyrat-Durebex, Pascal Reynier, Vincent Procaccio, Rudolf Hergesheimer, Philippe Corcia, Christian R Andres, Hélène Blasco
A ketogenic diet (KD) is a normocaloric diet composed by high fat (80-90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production...
2018: Frontiers in Molecular Neuroscience
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