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Synaptive Medical

Pasquale Striano, Vincenzo Belcastro, Antonietta Coppola, Carlo Minetti, Salvatore Striano
INTRODUCTION: Despite optimal medical treatment, up to 30% of patients with epilepsy continue to experience recurrent seizures, and the challenge for new more efficacious and better-tolerated drugs is continuing. New antiepileptic drugs include the evolution of preexisting drugs and new compounds identified through the investigation of additional molecular targets, such as SV2A synaptic vesicle protein, voltage-gated potassium channels, ionotropic and metabotropic glutamate receptors, and gap junctions...
October 5, 2016: Clinical Neuropharmacology
Natalia A Stefanova, Natalia A Muraleva, Kseniya Yi Maksimova, Ekaterina A Rudnitskaya, Elena Kiseleva, Darya V Telegina, Nataliya G Kolosova
Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals...
October 6, 2016: Aging
Claudio Blasi
The current treatment for obesity-related type 2 diabetes is not able to achieve sufficient metabolic control. New remission prospects have been offered through bariatric surgery and other interventional therapies. The aim of the study is to illustrate the mechanism by which such therapies affect the autonomic system, in particular the afferent vagal activity. The first and most important terminal of this activity is the brainstem vagal nucleus tractus solitarius. Its function, on which the vagal efferent inputs that control the splanchnic organs depend, is conditioned by the level of synaptic transmission within it...
October 11, 2016: Obesity Surgery
Man-Kyo Chung, Jennifer Park, Jamila Asgar, Jin Y Ro
BACKGROUND: Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined...
2016: Molecular Pain
Sarah A Wolfe, Emily R Workman, Chelcie F Heaney, Farr Niere, Sanjeev Namjoshi, Luisa P Cacheaux, Sean P Farris, Michael R Drew, Boris V Zemelman, R Adron Harris, Kimberly F Raab-Graham
Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium...
2016: Nature Communications
Dong Li, Hongjie Yuan, Xilma R Ortiz-Gonzalez, Eric D Marsh, Lifeng Tian, Elizabeth M McCormick, Gabrielle J Kosobucki, Wenjuan Chen, Anthony J Schulien, Rosetta Chiavacci, Anel Tankovic, Claudia Naase, Frieder Brueckner, Celina von Stülpnagel-Steinbeis, Chun Hu, Hirofumi Kusumoto, Ulrike B S Hedrich, Gina Elsen, Konstanze Hörtnagel, Elias Aizenman, Johannes R Lemke, Hakon Hakonarson, Stephen F Traynelis, Marni J Falk
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated cation channels that mediate excitatory synaptic transmission. Genetic mutations in multiple NMDAR subunits cause various childhood epilepsy syndromes. Here, we report a de novo recurrent heterozygous missense mutation-c.1999G>A (p.Val667Ile)-in a NMDAR gene previously unrecognized to harbor disease-causing mutations, GRIN2D, identified by exome and candidate panel sequencing in two unrelated children with epileptic encephalopathy. The resulting GluN2D p...
October 6, 2016: American Journal of Human Genetics
Junyeop Lee, Byung Gil Moon, Ah Ran Cho, Young Hee Yoon
PURPOSE: To investigate the structural integrity of the superficial capillary plexuses (SCPs) and deep capillary plexuses (DCPs) using optical coherence tomography (OCT) angiography (OCTA) in patients with diabetic macular edema (DME) and its association with the response to anti-vascular endothelial growth factor (VEGF) treatment. DESIGN: Retrospective, case-control study. PARTICIPANTS: We included 51 DME eyes with a poor response to anti-VEGF agents and 32 age-matched DME eyes with a good response to anti-VEGF treatment, along with 20 fellow eyes without DME from the cases and controls...
September 6, 2016: Ophthalmology
Samantha Palmer, Meghan C Towne, Phillip L Pearl, Renee C Pelletier, Casie A Genetti, Jiahai Shi, Alan H Beggs, Pankaj B Agrawal, Catherine A Brownstein
BACKGROUND: Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet...
July 28, 2016: Pediatric Neurology
Ravi Bansal, Xuejun Hao, Bradley S Peterson
We propose a method for segmenting brain tissue as either gray matter or white matter in the presence of varying tissue contrast, which can derive from either differential changes in tissue water content or increasing myelin content of white matter. Our method models the spatial distribution of intensities as a Markov Random Field (MRF) and estimates the parameters for the MRF model using a maximum likelihood approach. Although previously described methods have used similar models to segment brain tissue, accurate model of the conditional probabilities of tissue intensities and adaptive estimates of tissue properties to local intensities generates tissue definitions that are accurate and robust to variations in tissue contrast with age and across illnesses...
August 25, 2016: Magnetic Resonance Imaging
Seongkyun Kim, Hyoungkyu Kim, Jerald D Kralik, Jaeseung Jeong
Determining the fundamental architectural design of complex nervous systems will lead to significant medical and technological advances. Yet it remains unclear how nervous systems evolved highly efficient networks with near optimal sharing of pathways that yet produce multiple distinct behaviors to reach the organism's goals. To determine this, the nematode roundworm Caenorhabditis elegans is an attractive model system. Progress has been made in delineating the behavioral circuits of the C. elegans, however, many details are unclear, including the specific functions of every neuron and synapse, as well as the extent the behavioral circuits are separate and parallel versus integrative and serial...
August 2016: PLoS Computational Biology
Lili Cui, Dandan Wang, Sandra McGillis, Michele Kyle, Li-Ru Zhao
Stroke, a leading cause of adult disability in the world, is a severe medical condition with limited treatment. Physical therapy, the only treatment available for stroke rehabilitation, appears to be effective within 6 months post-stroke. Here, we have mechanistically determined the efficacy of combined two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF; SCF + G-CSF), in brain repair 6 months after cortical infarct induction in the transgenic mice carrying yellow fluorescent protein in Layer V pyramidal neurons (Thy1-YFP-H)...
June 2016: ASN Neuro
Julia N Bailey, Christopher Patterson, Laurence de Nijs, Reyna M Durón, Viet-Huong Nguyen, Miyabi Tanaka, Marco T Medina, Aurelio Jara-Prado, Iris E Martínez-Juárez, Adriana Ochoa, Yolli Molina, Toshimitsu Suzuki, María E Alonso, Jenny E Wight, Yu-Chen Lin, Laura Guilhoto, Elza Marcia Targas Yacubian, Jesús Machado-Salas, Andrea Daga, Kazuhiro Yamakawa, Thierry M Grisar, Bernard Lakaye, Antonio V Delgado-Escueta
PURPOSE: EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. METHODS: We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity...
July 28, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Daniel W Chung, Kenneth N Fish, David A Lewis
OBJECTIVE: Deficient excitatory drive to parvalbumin-containing cortical interneurons is proposed as a key neural substrate for altered gamma oscillations and cognitive dysfunction in schizophrenia. However, a pathological entity producing such a deficit has not been identified. The authors tested the hypothesis that cortical parvalbumin interneurons receive fewer excitatory synaptic inputs in individuals with schizophrenia. METHOD: Fluorescent immunohistochemistry, confocal microscopy, and post-image processing techniques were used to quantify the number of putative excitatory synapses (i...
July 22, 2016: American Journal of Psychiatry
Martin Picard, Douglas C Wallace, Yan Burelle
Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems...
September 2016: Mitochondrion
Bradley E Alger
With legal cannabis sales at $5.4 billion in 2015 and expected to rise by another billion this year in the United States, legalization and marijuana's impact on health is a hot topic of national debate. Casarett, a physician at the University of Pennsylvania, immerses himself in the culture, science, and smoke of medical marijuana in order to sort out the truth behind the buzz. Our reviewer, who has authored more than 120 research papers and reviews on the regulation of synaptic inhibition and endocannabinoids, tell us what the author got right, but also overlooked on his journey to learn more about a complex and controversial subject...
March 2016: Cerebrum: the Dana Forum on Brain Science
Anjana Silva, Sanjaya Kuruppu, Iekhsan Othman, Robert J A Goode, Wayne C Hodgson, Geoffrey K Isbister
Russell's vipers are snakes of major medical importance in Asia. Russell's viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell's viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations...
July 11, 2016: Neurotoxicity Research
Mattia Bramini, Silvio Sacchetti, Andrea Armirotti, Anna Rocchi, Ester Vázquez, Verónica León Castellanos, Tiziano Bandiera, Fabrizia Cesca, Fabio Benfenati
Graphene has the potential to make a very significant impact on society, with important applications in the biomedical field. The possibility to engineer graphene-based medical devices at the neuronal interface is of particular interest, making it imperative to determine the biocompatibility of graphene materials with neuronal cells. Here we conducted a comprehensive analysis of the effects of chronic and acute exposure of rat primary cortical neurons to few-layer pristine graphene (GR) and monolayer graphene oxide (GO) flakes...
July 26, 2016: ACS Nano
Ian A Meinertzhagen
The brain is a network of neurons, one that generates behaviour, and knowing the former is crucial to understanding the latter. Identifying the exact network of synaptic connections, or connectome, of the fly's central nervous system is now a major objective in Drosophila neurobiology, one that has been initiated in several laboratories, especially the Janelia Research Campus of the Howard Hughes Medical Institute. Progress is most advanced in the optic neuropiles of the visual system. The effort to derive a connectome from these and other neuropile regions is proceeding by various methods of electron microscopy, especially focused-ion beam milling scanning electron microscopy, and relies upon - but is to be carefully distinguished from - published light microscopic methods that reveal the projections of genetically labelled cell types...
June 2016: Journal of Neurogenetics
Mehmet Cansev
Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory rodents with uridine, DHA and choline enhances the amount of brain membranes as well as synaptic proteins and increases the number of dendritic spines, the essential cytological precursor of new synapses...
September 2016: Neuromolecular Medicine
Adriano A Cattani, Camille Allene, Volker Seifert, Felix Rosenow, David C Henshall, Thomas M Freiman
Patients who have sustained brain injury or had developmental brain lesions present a non-negligible risk for developing delayed epilepsy. Finding therapeutic strategies to prevent development of epilepsy in at-risk patients represents a crucial medical challenge. Noncoding microRNA molecules (miRNAs) are promising candidates in this area. Indeed, deregulation of diverse brain-specific miRNAs has been observed in animal models of epilepsy as well as in patients with epilepsy, mostly in temporal lobe epilepsy (TLE)...
July 2016: Epilepsia
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