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https://www.readbyqxmd.com/read/28737479/evaluation-of-brivaracetam-a-new-drug-to-treat-epilepsy
#1
Jasmina R Milovanović, Slobodan M Janković, Ana Pejčić, Miloš Milosavljević, Valentina Opančina, Vesela Radonjić, Zoran Protrka, Marina Kostić
High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered. Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy...
July 24, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28734961/radix-puerariae-modulates-glutamatergic-synaptic-architecture-and-potentiates-functional-synaptic-plasticity-in-primary-hippocampal-neurons
#2
Mohammad Maqueshudul Haque Bhuiyan, Md Nazmul Haque, Md Mohibbullah, Yung Kyu Kim, Il Soo Moon
ETHNOPHARMACOLOGICAL RELEVANCE: Neurologic disorders are frequently characterized by synaptic pathology, including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Therefore, to promote and/or protect synapses by the use of natural molecules capable of modulating neurodevelopmental events, such as, spinogenesis and synaptic plasticity, could offer a preventive and curative strategy for nervous disorders associated with synaptic pathology...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28734834/dynein-binds-and-stimulates-axonal-motility-of-the-endosome-adaptor-and-neep21-family-member-calcyon
#3
Liang Shi, Nagendran Muthusamy, Deanna Smith, Clare Bergson
The neuron-enriched, endosomal protein Calcyon (Caly) regulates endocytosis and vesicle sorting, and is important for synaptic plasticity and brain development. In the current investigation of Caly interacting proteins in brain, the microtubule retrograde motor subunit, cytoplasmic dynein 1 heavy chain (DYNC1H), and microtubule structural proteins, α and β tubulin, were identified as Caly associated proteins by MALDI-ToF/ToF. Direct interaction of the Caly-C terminus with dynein and tubulin was further confirmed in in vitro studies...
July 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28731329/generation-and-characterization-of-anti-vglut-nanobodies-acting-as-inhibitors-of-transport
#4
Stephan Schenck, Laura Kunz, Daniela Sahlender, Els Pardon, Eric R Geertsma, Iaroslav Savtchouk, Toshiharu Suzuki, Yvonne Neldner, Saša Štefanić, Jan Steyaert, Andrea Volterra, Raimund Dutzler
The uptake of glutamate by synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). The central role of these transporters in excitatory neurotransmission underpins their importance as pharmacological targets. Although several compounds inhibit VGLUTs, highly specific inhibitors were so far unavailable, thus limiting applications to in vitro experiments. Besides their potential in pharmacology, specific inhibitors would also be beneficial for the elucidation of transport mechanisms. To overcome this shortage, we generated nanobodies (Nbs) by immunization of a llama with purified rat VGLUT1 and subsequent selection of binders from a phage display library...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28726749/ladder-shaped-ion-channel-ligands-current-state-of-knowledge
#5
REVIEW
Yuri B Shmukler, Denis A Nikishin
Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of Gambierdiscus and Karenia genera, correspondingly. Ciguatera, evoked by CTXs, is a type of ichthyosarcotoxism, which involves a variety of gastrointestinal and neurological symptoms, while BTXs cause so-called neurotoxic shellfish poisoning. Both types of toxins are reviewed together because of similar mechanisms of their action. These are the only molecules known to activate voltage-sensitive Na⁺-channels in mammals through a specific interaction with site 5 of its α-subunit and may compete for it, which results in an increase in neuronal excitability, neurotransmitter release and impairment of synaptic vesicle recycling...
July 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28726234/-current-status-of-congenital-myasthenic-syndromes
#6
REVIEW
M Bestue-Cardiel, D Natera-de Benito
Since Engel reported the first case of congenital myasthenia in 1977 and the first pathogenic gene was found in 1995, knowledge about congenital myasthenic syndromes has continued to grow. Over the years, the pathogenic basis, its clinical features, the phenotype-genotype correlations that have been established and its therapeutic management have all been described. In this group of diseases the safety margin of neuromuscular transmission is altered by different mechanisms: in the synthesis or storage of acetylcholine quanta in the synaptic vesicles, in the calcium-mediated release of acetylcholine in the nerve terminal or in the efficiency of the quantum released to generate a post-synaptic depolarisation...
August 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28725181/impact-of-proestrus-on-gene-expression-in-the-medial-preoptic-area-of-mice
#7
Csaba Vastagh, Zsolt Liposits
The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that-via wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28724748/depressed-synaptic-transmission-and-reduced-vesicle-release-sites-in-huntington-s-disease-neuromuscular-junctions
#8
Ahmad Khedraki, Eric J Reed, Shannon H Romer, Qingbo Wang, William Romine, Mark M Rich, Robert J Talmadge, Andrew A Voss
Huntington's disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the central nervous system. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28718905/a-novel-cell-cell-communication-mechanism-in-the-nervous-system-exosomes
#9
REVIEW
Guan Zhang, Ping Yang
Exosomes are small extracellular membrane-based vesicles with a variety of cargoes that are involved in numerous physiological and pathological processes in the nervous system. Accumulating evidence has implicated that exosomes are emerging as a novel form of intercellular communication within the nervous system. In this review, we first illustrate exosome metabolism including its formation, secretion, transport, and uptake. Second, we compare exosomes to synaptic vesicles in terms of intercellular messengers and communicators...
July 18, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#10
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28711655/ubiquitination-at-the-mitochondria-in-neuronal-health-and-disease
#11
REVIEW
Christian Covill-Cooke, Jack Howden, Nicol Birsa, Josef Kittler
The preservation of mitochondrial function is of particular importance in neurons given the high energy requirements of action potential propagation and synaptic transmission. Indeed, disruptions in mitochondrial dynamics and quality control are linked to cellular pathology in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Here, we will discuss the role of ubiquitination by the E3 ligases: Parkin, MARCH5 and Mul1, and how they regulate mitochondrial homeostasis. Furthermore, given the role of Parkin and Mul1 in the formation of mitochondria-derived vesicles we give an overview of this area of mitochondrial homeostasis...
July 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28710481/the-lrrk2-g2385r-variant-is-a-partial-loss-of-function-mutation-that-affects-synaptic-vesicle-trafficking-through-altered-protein-interactions
#12
Maria Dolores Perez Carrion, Silvia Marsicano, Federica Daniele, Antonella Marte, Francesca Pischedda, Eliana Di Cairano, Ester Piovesana, Felix von Zweydorf, Elisabeth Kremmer, Christian Johannes Gloeckner, Franco Onofri, Carla Perego, Giovanni Piccoli
Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson's disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed the functional features attributed to LRRK2 by its N- and C-terminal domains. We combined TIRF microscopy and synaptopHluorin assay to visualize synaptic vesicle trafficking. We found that N- and C-terminal domains have opposite impact on synaptic vesicle dynamics...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710284/the-neuronal-protein-neurexin-directly-interacts-with-the-scribble-pix-complex-to-stimulate-f-actin-assembly-for-synaptic-vesicle-clustering
#13
Menglong Rui, Jinjun Qian, Lijuan Liu, Yihan Cai, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neuro-transmission. However, how SV cluster in particular synaptic compartments to maintain normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidences suggest that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28707873/light-activation-of-calcein-inhibits-vesicle-release-of-catecholamines
#14
Brooke A Miller, Jason B Papke, Vytas P Bindokas, Amy B Harkins
Calcein, a fluorescent fluid phase marker, has been used to track and visualize cellular processes such as synaptic vesicle fusion. It is also the fluorophore for Live cells in the commonly used Live/Dead viability assay. In pilot studies designed to determine fusion pore open size and vesicle movement in secretory cells, imaging analysis revealed that calcein reduced the number of vesicles released from the cells when stimulated with nicotine. Using amperometry to detect individual vesicle release events, we show that when calcein is present in the media, the number of vesicles that fuse with the cellular membrane are reduced when cells are stimulated with either nicotine or high K+...
July 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28705267/acrylamide-induced-subacute-neurotoxic-effects-on-the-cerebral-cortex-and-cerebellum-at-the-synapse-level-in-rats
#15
Bin Zhang, Hua Shao, Xiu Hui Wang, Xiao Chen, Zhong Sheng Li, Peng Cao, Dan Zhu, Yi Guang Yang, Jing Wei Xiao, Bin Li
OBJECTIVE: To investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats. METHODS: Thirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy...
June 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28701919/amyloid-%C3%AE-impairs-vesicular-secretion-in-neuronal-and-astrocyte-peptidergic-transmission
#16
Virginia Plá, Neus Barranco, Esther Pozas, Fernando Aguado
Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-β (Aβ) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer's disease (AD). Here, we analyze the impact of soluble Aβ1-42 assemblies on peptidergic secretion in cortical neurons and astrocytes. We show that neurons and astrocytes differentially produce and release carboxypeptidase E (CPE) and secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to the regulated secretory pathway...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28701482/analysis-of-rim-expression-and-function-at-mouse-photoreceptor-ribbon-synapses
#17
Martina Löhner, Norbert Babai, Tanja Müller, Kaspar Gierke, Jenny Atorf, Anneka Joachimsthaler, Angela Peukert, Henrik Martens, Andreas Feigenspan, Jan Kremers, Susanne Schoch, Johann Helmut Brandstätter, Hanna Regus-Leidig
RIM (RAB3A-interacting molecule) proteins are important regulators of transmitter release from active zones. At conventional chemical synapses, RIMs contribute substantially to vesicle priming and docking, and their loss reduces the readily releasable pool of synaptic vesicles by up to 75 %. The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca(2+) channels and the fusion site, and activates Munc13. We reported previously that at mouse photoreceptor ribbon synapses vesicle priming is Munc13-independent...
July 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28700922/the-functional-amyloid-orb2a-binds-to-lipid-membranes
#18
Maria A Soria, Silvia A Cervantes, Thalia H Bajakian, Ansgar B Siemer
Lipid membranes interact with and influence the aggregation of many amyloid-forming proteins. Orb2 is a cytoplasmic polyadenylation element-binding protein homolog in Drosophila melanogaster that forms functional amyloids necessary for long-term memory. One isoform, Orb2A, has a unique N-terminus that has been shown to be important for the formation of amyloid-like aggregates and long-term memory in vivo. Orb2A is also found enriched in the synaptic membrane fraction. Our sequence and hydropathy analysis suggests that it can form an amphipathic helix, which is ideal for lipid membrane interaction...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28698583/ammonium-chloride-alters-neuronal-excitability-and-synaptic-vesicle-release
#19
Roman M Lazarenko, Claire E DelBove, Claire E Strothman, Qi Zhang
Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH changes to fluorescent signals. For imaging and analysis purposes, high concentration ammonium chloride is routinely used to alkalize intracellular membrane compartments under the assumption that it does not cause long-term effects on cellular processes being studied like neurotransmission. However, pathological studies about hyperammonemia have shown that ammonium is toxic to brain cells especially astrocytes and neurons...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698220/activation-of-camkiv-by-soluble-amyloid-%C3%AE-1-42-impedes-trafficking-of-axonal-vesicles-and-impairs-activity-dependent-synaptogenesis
#20
Daehun Park, Myeongsu Na, Jung Ah Kim, Unghwi Lee, Eunji Cho, Mirye Jang, Sunghoe Chang
The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ1-42 prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ1-42 impaired Ca(2+) clearance from presynaptic terminals and increased the basal Ca(2+) concentration...
July 11, 2017: Science Signaling
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