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Sudarat Nimitvilai, Joachim D Uys, John J Woodward, Patrick K Randall, Lauren E Ball, Robert W Williams, Byron C Jones, Lu Lu, Kathleen A Grant, Patrick J Mulholland
Cognitive impairments, uncontrolled drinking, and neuropathological cortical changes characterize alcohol use disorder. Dysfunction of the orbitofrontal cortex (OFC), a critical cortical subregion that controls learning, decision-making, and prediction of reward outcomes, contributes to executive cognitive function deficits in alcoholic individuals. Electrophysiological and quantitative synaptomics techniques were used to test the hypothesis that heavy drinking produces neuroadaptations in the macaque OFC. Integrative bioinformatics and reverse genetic approaches were used to identify and validate synaptic proteins with novel links to heavy drinking in BXD mice...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Keita Satoh, Keiko Takanami, Kazuyoshi Murata, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto
This data article contains complementary figure and movies (Supplementary Movies 1-3) related to the research article entitled, "Effective synaptome analysis of itch-mediating neurons in the spinal cord: a novel immunohistochemical methodology using high-voltage electron microscopy" [7]. It is important to show the synaptic connections at the ultrastructural level to understand the neural circuit, which requires the three-dimensional (3-D) analyses in the electron microscopy. Here, we applied a new sample preparation method, a high-contrast en bloc staining according to the protocol of the National Center for Microscopy and Imaging Research (NCMIR), University of California, San Diego, CA, USA to high-voltage electron microscopy (HVEM) tomography in order to examine the 3-D chemical neuroanatomy of the rat spinal cord...
September 2015: Data in Brief
M Pirooznia, T Wang, D Avramopoulos, J B Potash, P P Zandi, F S Goes
Major depressive disorder (MDD) is among the leading causes of worldwide disability. Despite its significant heritability, large-scale genome-wide association studies (GWASs) of MDD have yet to identify robustly associated common variants. Although increased sample sizes are being amassed for the next wave of GWAS, few studies have as yet focused on rare genetic variants in the study of MDD. We sequenced the exons of 1742 synaptic genes previously identified by proteomic experiments. PLINK/SEQ was used to perform single variant, gene burden and gene set analyses...
May 2016: Molecular Psychiatry
Keita Satoh, Keiko Takanami, Kazuyoshi Murata, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto
Transmission electron microscopy (TEM) is used for three-dimensional (3-D) analysis of synaptic connections in neuroscience research. However, 3-D reconstruction of the synapses using serial ultrathin sections is a powerful but tedious approach requiring advanced technical skills. High-voltage electron microscopy (HVEM) allows examination of thicker sections of biological specimens due to the increased penetration of the more accelerated electrons, which is useful to analyze the 3-D structure of biological specimens...
July 10, 2015: Neuroscience Letters
Pablo Henny, Matthew T C Brown, Benjamin R Micklem, Peter J Magill, J Paul Bolam
Determining the number and placement of synaptic inputs along the distinct plasma membrane domains of neurons is essential for explaining the basis of neuronal activity and function. We detail a strategy that combines juxtacellular labeling, neuronal reconstructions and stereological sampling of inputs at the ultrastructural level to define key elements of the afferent 'synaptome' of a given neuron. This approach provides unbiased estimates of the total number and somato-dendritic distribution of synapses made with individual neurons...
March 2014: Brain Structure & Function
Seth G N Grant
The human synapse proteome is a highly complex collection of proteins that is disrupted by hundreds of gene mutations causing over 100 brain diseases. These synaptic diseases, or synaptopathies, cause major psychiatric, neurological and childhood developmental disorders through mendelian and complex genetic mechanisms. The human postsynaptic proteome and its core signaling complexes built by the assembly of receptors and enzymes around Membrane Associated Guanylate Kinase (MAGUK) scaffold proteins are a paradigm for systematic analysis of synaptic diseases...
June 2012: Current Opinion in Neurobiology
Mehdi Pirooznia, Tao Wang, Dimitrios Avramopoulos, David Valle, Gareth Thomas, Richard L Huganir, Fernando S Goes, James B Potash, Peter P Zandi
MOTIVATION: The synapse is integral to the function of the brain and may be an important source of dysfunction underlying many neuropsychiatric disorders. Consequently, it is an excellent candidate for large-scale genomic and proteomic study. However, while the tools and databases available for the annotation of high-throughput DNA and protein are generally robust, a comprehensive resource dedicated to the integration of information about the synapse is lacking. RESULTS: We present an integrated database, called SynaptomeDB, to retrieve and annotate genes comprising the synaptome...
March 15, 2012: Bioinformatics
Javier DeFelipe
A major challenge in neuroscience is to decipher the structural layout of the brain. The term "connectome" has recently been proposed to refer to the highly organized connection matrix of the human brain. However, defining how information flows through such a complex system represents so difficult a task that it seems unlikely it could be achieved in the near future or, for the most pessimistic, perhaps ever. Circuit diagrams of the nervous system can be considered at different levels, although they are surely impossible to complete at the synaptic level...
November 26, 2010: Science
Verónica Pérez-De La Cruz, Mina Konigsberg, José Pedraza-Chaverri, Nieves Herrera-Mundo, Mauricio Díaz-Muñoz, Julio Morán, Teresa Fortoul-van der Goes, Adrián Rondán-Zárate, Perla D Maldonado, Syed F Ali, Abel Santamaría
Excessive calcium is responsible for triggering different potentially fatal metabolic pathways during neurodegeneration. In this study, we evaluated the role of calcium on the oxidative damage produced in an in vitro combined model of excitotoxicity/energy deficit produced by the co-administration of quinolinate and 3-nitropropionate to brain synaptosomal membranes. Synaptosomal fractions were incubated in the presence of subtoxic concentrations of these agents (21 and 166 microm, respectively). In order further to characterize possible toxic mechanisms involved in oxidative damage in this experimental paradigm, agents with different properties - dizocilpine, acetyl L-carnitine, iron porphyrinate and S-allylcysteine - were tested at increasing concentrations (10-1000 microm)...
March 2008: European Journal of Neuroscience
Daniel J Müller, James L Kennedy
Classic and modern antipsychotics can induce substantial weight gain causing diabetes, lipid abnormalities and psychological distress. Treatment emergent weight gain varies within the broad class of antipsychotics; however, an individual's propensity to develop weight gain largely depends on genetic factors. The first part of this review highlights current ideas and concepts related to antipsychotic-induced weight gain, including principles on energy homeostasis. The second part summarizes genetic findings emphasizing studies published after 2003 as prior studies have been reviewed in detail elsewhere...
September 2006: Pharmacogenomics
D Jerusalinsky, E Kornisiuk, R Bernabeu, I Izquierdo, C Cerveñansky
The venom of some Dendroaspis snakes contains small proteins (7500 mol. wt) that inhibit the binding of radiolabelled muscarinic antagonist to brain synaptomal membranes. There were no peptides described among muscarinic ligands until Adem et al. (Biochim. biophys. Acta 968, 340-345, 1988) reported that muscarinic toxins (MTxs), MTx1 and 2 were able to inhibit 3H-QNB binding to rat brain membranes. Since MTxs inhibit around half of specific binding of 3H-quinuclidinyl benzilate (3H-QNB) and 3H-N-methyl-scopolamine (3H-NMS), which do not discriminate between subtypes of muscarinic receptors, it has been proposed that MTxs might selectively bind to some subtype...
April 1995: Toxicon: Official Journal of the International Society on Toxinology
P M Borodin
A triple synaptomal complex was observed between 3 small-sized chromosomes in 4 spermatocytes closely connected by intercellular bridges, of the common vole (Microtus arvalis L.). Other spermatocytes from the same and from 2 other males had a normal chromosome complement and pairing patterns. This finding was interpreted as the result of a single act of non-disjunction taking place in a spermatogonium. These data suggest that chromosome non-disjunction in premeiotic germ cells can be considered one of the causes of aneuploidy in mammals...
January 1991: Mutation Research
N I Maĭsov, N S Tolmacheva, K S Raevskiĭ
The influence of a number of neuroleptics and antidepressants on the release of 3H-GABA from the synaptosomas of the cerebral cortex in rats was studied. Chlorpromazine, phthorphenazine, trifluperidol, imipramine, phthoracizine caused an intensified liberation of 3H-GABA from the synaptosomas. In this phenothiazine neuroleptics proved more active than did trifluperidol and antidepressants. New neuroleptics--azabuperon and carbidine and also diphenylhydantoin tended to restrict the liberation of the mediator from synaptosomas...
September 1976: Farmakologiia i Toksikologiia
R Mansner
The in vitro uptake of nicotine into the crude synaptosomal fraction of rat brain and spinal cord was studied. The tissue/midium ratio was low and the changing of incubation time or [14C]nicotine concentration did not affect the ratio, nor did a metabolic inhibitor, sodium fluoride. A lowered ratio was obtained at 0degrees C, but this decrease may be attributable to an altered pKa of the drug at low temperature. Nicotine antagonists, mecamylamine and hexamethonium, did not affect the ratio when incubating the crude synaptosomal fraction of either adult or infant rat brain...
August 1977: Medical Biology
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