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Synaptive Medical

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
R L Blakemore, M R Mac Askill, 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)...
March 6, 2018: Neuropsychologia
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
Natasha Warikoo, Samuel J Brunwasser, Ann Benz, Hong-Jin Shu, Steven M Paul, Michael Lewis, James Doherty, Michael Quick, 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 central nervous system associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to cerebrospinal fluid (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...
February 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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 19, 2018: Neuropharmacology
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
Yazan S Batarseh, Amal Kaddoumi
Previous evidence suggested that extra-virgin olive oil (EVOO) is linked to attenuating amyloid-β (Aβ) pathology and improving cognitive function in Alzheimer's disease (AD) mouse models. In addition, we recently reported the beneficial effect of oleocanthal, a phenolic compound in EVOO, against AD pathology. Currently, medications available to target AD pathology are limited. Donepezil is an acetylcholine esterase inhibitor approved for use for all AD stages. Donepezil has been reported to have limited Aβ-targeting mechanisms beside its acetylcholine esterase inhibition...
December 27, 2017: Journal of Nutritional Biochemistry
Martina von Wilmsdorff, Fabian Manthey, Marie-Luise Bouvier, Oliver Staehlin, Peter Falkai, Eva Meisenzahl-Lechner, Andrea Schmitt, Peter J Gebicke-Haerter
We investigated the effects of clozapine and haloperidol, drugs that are widely used in the treatment of schizophrenia, on gene expression in six cortical and subcortical brain regions of adult rats. Drug treatments started at postnatal day 85 and continued over a 12-week period. Ten animals received haloperidol (1 mg/kg bodyweight) and ten received clozapine (20 mg/kg bodyweight) orally each day. Ten control rats received no drugs. The ten genes selected for this study did not belong to the dopaminergic or serotoninergic systems, which are typically targeted by the two substances, but coded for proteins of the cytoskeleton and proteins belonging to the synaptic transmitter release machinery...
February 5, 2018: European Archives of Psychiatry and Clinical Neuroscience
Joseph P Schacht, Konstantin E Voronin, Patrick K Randall, Raymond F Anton
Dopamine (DA) signaling regulates many aspects of Alcohol Use Disorder (AUD). However, clinical studies of dopaminergic medications, including the DA partial agonist aripiprazole (APZ), have been inconsistent, suggesting the possibility of a pharmacogenetic interaction. This study examined whether variation in DA-related genes moderated APZ effects on reward-related AUD phenotypes. The interacting effects of APZ and a variable number tandem repeat (VNTR) polymorphism in DAT1/SLC6A3 (the gene encoding the DA transporter (DAT)) were tested...
December 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Bin Yi, Cong Wu, Runjie Shi, Kun Han, Haibin Sheng, Bei Li, Ling Mei, Xueling Wang, Zhiwu Huang, Hao Wu
HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity...
March 2018: Otology & Neurotology
Shibeshih Belachew
Shibeshih Belachew speaks to Laura Dormer, Commissioning Editor: Dr Shibeshih Belachew, MD, PhD, is a Senior Medical Director for Multiple Sclerosis (MS) Disease Area in Global Product Development Medical Affairs at Roche (Basel, Switzerland). Prior to joining Roche in January 2016, he was Director of MS Franchise and Head of Medical Director's office for Biogen Region Europe and Canada. Previously at Biogen he also served as a Director in Global Neurology for the natalizumab program in Cambridge (MA, USA)...
January 5, 2018: Neurodegenerative Disease Management
Nathalie T Sanon, Jonathan Gagné, Daniele C Wolf, Soumia Aboulamer, Ciprian M Bosoi, Alexe Simard, Estelle Messiet, Sébastien Desgent, Lionel Carmant
Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors...
December 26, 2017: Epilepsy & Behavior: E&B
John H Brock, Lori Graham, Eileen Staufenberg, Sarah Im, Mark H Tuszynski
Previously others and we have shown that rodent neural progenitor cells (NPCs) can support functional recovery following cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral mid-cervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived neural progenitor cells were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts...
December 26, 2017: Journal of Neurotrauma
Kin Ying Wong, Choo Hock Tan, Kae Yi Tan, Quraishi H Naeem, Nget Hong Tan
Naja naja is a medically important species that is distributed widely in South Asia. Its venom lethality and neutralization profile have been reported to vary markedly, but the understanding of this phenomenon has been limited without a comprehensive venom profile for the Pakistani N. naja. This study set to investigate the venom proteome of Pakistani N. naja applying reverse-phase HPLC, SDS-PAGE, mass spectrometry and data-mining approaches. The venom enzymatics and antigen binding activities were also studied...
December 23, 2017: Journal of Proteomics
Kristen Ward, Leslie Citrome
The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing...
February 2018: Expert Opinion on Drug Metabolism & Toxicology
Maria Skibinska, Pawel Kapelski, Aleksandra Rajewska-Rager, Joanna Pawlak, Aleksandra Szczepankiewicz, Beata Narozna, Joanna Twarowska-Hauser, Monika Dmitrzak-Weglarz
BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development, as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of psychiatric disorders and its serum level is a potential biomarker for depression. The aim of this study was to examine serum levels of BDNF in first-episode depression and its correlation with clinical and metabolic parameters. MATERIALS AND METHODS: The study was performed on a group of 60 women: 30 diagnosed with a first-episode of depression and 30 healthy controls...
April 2018: Nordic Journal of Psychiatry
Muhammad Waqas, Syed Ather Enam, Fauzan A Hashmi, Fatima Mubarak, Fazal Arain
High-grade gliomas possess internal pathological heterogeneity. Selective sampling of different tumor regions can help in the study of this heterogeneity. In this report, we have described the use of a novel navigation and optical system for the selective regional sampling of a high-grade glioma lesion. A 45-year-old gentleman presented to us with complaints of intermittent frontal headaches for past eight months. On examination, he had subtle pyramidal weakness in left upper and lower extremities. Magnetic resonance imaging (MRI) showed a large contrast-enhancing, space-occupying lesion in the right frontal lobe causing perilesional edema and midline shift...
October 2, 2017: Curēus
Angelo Blasio, Jingyi Wang, Dan Wang, Florence P Varodayan, Matthew B Pomrenze, Jacklyn Miller, Anna M Lee, Thomas McMahon, Sandeep Gyawali, Hua-Yu Wang, Marisa Roberto, Stanton McHardy, Michael A Pleiss, Robert O Messing
BACKGROUND: Despite the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, underscoring the need for new, effective medications. Previous results using protein kinase C epsilon (PKCε) knockout mice, RNA interference against PKCε, and peptide inhibitors of PKCε predict that small-molecule inhibitors of PKCε should reduce alcohol consumption in humans. METHODS: We designed a new class of PKCε inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor Y-27632...
December 1, 2017: Biological Psychiatry
Vijay Agarwal, James G Malcolm, Gustavo Pradilla, Daniel L Barrow
We present a case of intraventricular meningioma resected via a transcortical approach using tractography for optic radiation and arcuate fasciculus preservation. We include a review of the literature. A 54-year-old woman with a history of breast cancer presented with gait imbalance. Workup revealed a mass in the atrium of the left lateral ventricle consistent with a meningioma. Whole brain automated diffusion tensor imaging (DTI) was used to plan a transcortical resection while sparing the optic radiations and arcuate fasciculus...
September 28, 2017: Curēus
Muhammad Waqas, Ayesha Siddiqui, Fatima Mubarak, Syed Ather Enam
Non-ruptured arteriovenous malformations (AVMs) rarely cause tract disruption. Few studies have described how ruptured AVMs influence white matter (WM) tract morphology. We reviewed consecutive AVM cases treated at a tertiary care hospital where diffusion tensor imaging (DTI) tractography was obtained preoperatively. DTI was performed using the Synaptive Plan (Synaptive Medical Inc., Toronto, Canada). Quality control was performed by clinical application specialist. Perinidal fractional anisotropy (FA) value of corticospinal tracts (CST) was obtained...
September 28, 2017: Curēus
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