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https://www.readbyqxmd.com/read/28432980/discovery-of-potential-inhibitor-against-human-acetylcholinesterase-a-molecular-docking-and-molecular-dynamics-investigation
#1
Surya Pratap Singh, Dwijendra Gupta
Alzheimer's disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE...
April 12, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28432601/neuropathic-pain-central-vs-peripheral-mechanisms
#2
REVIEW
Kathleen Meacham, Andrew Shepherd, Durga P Mohapatra, Simon Haroutounian
PURPOSE OF REVIEW: Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial...
June 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28432486/cholesterol-as-a-modifying-agent-of-the-neurovascular-unit-structure-and-function-under-physiological-and-pathological-conditions
#3
REVIEW
Ewelina Czuba, Aleksandra Steliga, Grażyna Lietzau, Przemysław Kowiański
The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules...
April 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28432360/functional-ectopic-neuritogenesis-by-retinal-rod-bipolar-cells-is-regulated-by-mir-125b-5p-during-retinal-remodeling-in-rcs-rats
#4
Yan Fu, Baoke Hou, Chuanhuang Weng, Weiping Liu, Jiaman Dai, Congjian Zhao, Zheng Qin Yin
Following retinal degeneration, retinal remodeling can cause neuronal microcircuits to undergo structural alterations, which particularly affect the dendrites of bipolar cells. However, the mechanisms and functional consequences of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats as a model of retinal degeneration, to study structural changes in rod bipolar cells (RBCs) and the underlying mechanisms of these changes. We found that, with retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) of the retina, and the ectopic dendrites formed synapses with the remaining photoreceptors...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432303/closed-loop-deep-brain-stimulation-by-pulsatile-delayed-feedback-with-increased-gap-between-pulse-phases
#5
Oleksandr V Popovych, Borys Lysyansky, Peter A Tass
Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432301/ampk-signaling-in-the-nucleus-accumbens-core-mediates-cue-induced-reinstatement-of-cocaine-seeking
#6
Xue-Jiao Gao, Kai Yuan, Lu Cao, Wei Yan, Yi-Xiao Luo, Min Jian, Jian-Feng Liu, Qin Fang, Ji-Shi Wang, Ying Han, Jie Shi, Lin Lu
Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#7
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#8
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432141/the-spacing-effect-for-structural-synaptic-plasticity-provides-specificity-and-precision-in-plastic-changes
#9
Martin A San, L Rela, B D Gelb, M R Pagani
In contrast to trials of training without intervals (massed training), training trials spaced over time (spaced training) induce a more persistent memory identified as long-term memory (LTM). This phenomenon known as "the spacing effect for memory" is poorly understood. LTM is supported by structural synaptic plasticity; however, how synapses integrate spaced stimuli remains elusive. Here, we analyzed events of structural synaptic plasticity at the single synapse level after distinct patterns of stimulation in motoneurons of Drosophila We found that the spacing effect is a phenomenon detected at synaptic level, which determine the specificity and the precision in structural synaptic plasticity...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432140/visually-evoked-3-5-hz-membrane-potential-oscillations-reduce-the-responsiveness-of-visual-cortex-neurons-in-awake-behaving-mice
#10
Michael C Einstein, Pierre-Olivier Polack, Duy T Tran, Peyman Golshani
Low frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low frequency Vm oscillations have been described in inactive awake animals, but it is unclear if they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432137/dissociation-of-choice-formation-and-choice-correlated-activity-in-macaque-visual-cortex
#11
Robbe L T Goris, Corey M Ziemba, Gabriel M Stine, Eero P Simoncelli, J Anthony Movshon
Responses of individual task-relevant sensory neurons can predict monkeys' trial-by-trial choices in perceptual decision-making tasks. Choice-correlated activity has been interpreted as evidence that the responses of these neurons are causally linked to perceptual judgements. To further test this hypothesis, we studied responses of orientation-selective neurons in V1 and V2 while two macaque monkeys performed a fine orientation discrimination task. Although both animals exhibited a high level of neuronal and behavioral sensitivity, only one exhibited choice-correlated activity...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432124/regulation-of-neurite-morphogenesis-by-interaction-between-r7-regulator-of-g-protein-signaling-complexes-and-g-protein-subunit-g%C3%AE-13
#12
Stephanie L Scherer, Matthew D Cain, Stanley M Kanai, Kevin M Kaltenbronn, Kendall J Blumer
The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of Gi/o α-subunits, several neurological phenotypes of R7-RGS knockout mice are not readily explained by dysregulated Gi/o signaling...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432032/neuronal-excitation-and-permeabilization-by-200-ns-pulsed-electric-field-an-optical-membrane-potential-study-with-fluovolt-dye
#13
Andrei G Pakhomov, Iurii Semenov, M Casciola, Shu Xiao
Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca(2+) signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28432022/a-crosstalk-between-muscarinic-and-crf2-receptors-regulates-cellular-adhesion-properties-of-human-colon-cancer-cells
#14
M Pelissier-Rota, N T Chartier, B Bonaz, M R Jacquier-Sarlin
Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#15
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431685/galr3-mediates-galanin-proliferative-effects-on-postnatal-hippocampal-precursors
#16
D Khan, M Khan, Johan Runesson, M Zaben, W P Gray
Galanin, a neuropeptide co-released from noradrenergic and serotonergic projection neurons to the dentate gyrus, has recently emerged as an important mediator for signaling neuronal activity to the subgranular neurogenic stem cell niche supporting adult hippocampal neurogenesis. Galanin and its receptors appear to play key roles in depression-like behavior, and effects on hippocampal neurogenesis are relevant to pharmacological strategies for treating depression, which in part appear to rely on restoring altered neurogenesis...
April 5, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28431434/bright-light-suppresses-form-deprivation-myopia-development-with-activation-of-dopamine-d1-receptor-signaling-in-the-on-pathway-in-retina
#17
Si Chen, Zhina Zhi, Qingqing Ruan, Qingxia Liu, Fen Li, Fen Wan, Peter S Reinach, Jiangfan Chen, Jia Qu, Xiangtian Zhou
Purpose: To determine whether dopamine receptor D1 (D1R) signaling pathway activation by bright light (BL) in specific retinal neuronal cell types contributes to inhibiting form-deprivation myopia (FDM) in mice. Methods: Mice (3-weeks old) were raised under either normal light (NL: 100-200 lux) or BL (2500-5000 lux) conditions with or without form deprivation. Refraction changes were evaluated with an eccentric infrared photorefractor, and ocular axial components with optical coherence tomography...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#18
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430937/high-sugar-but-not-high-fat-food-activates-supraoptic-oxytocin-neurones-in-the-male-rat
#19
Catherine Hume, Nancy Sabatier, John Menzies
Oxytocin is a potent anorexigen and is believed to have a role in satiety signalling. We developed rat models to study the activity of oxytocin neurones in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology.Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurones expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anaesthetised rats with SCM...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#20
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
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