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https://www.readbyqxmd.com/read/29452226/quantitative-proteomic-analysis-reveals-synaptic-dysfunction-in-the-amygdala-of-rats-susceptible-to-chronic-mild-stress
#1
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2,562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29449585/electrical-coupling-between-a17-cells-enhances-reciprocal-inhibitory-feedback-to-rod-bipolar-cells
#2
Claudio Elgueta, Felix Leroy, Alex H Vielma, Oliver Schmachtenberg, Adrian G Palacios
A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449458/a-barnes-maze-for-juvenile-rats-delineates-the-emergence-of-spatial-navigation-ability
#3
Daniel G McHail, Nazanin Valibeigi, Theodore C Dumas
The neural bases of cognition may be greatly informed by relating temporally defined developmental changes in behavior with concurrent alterations in neural function. A robust improvement in performance in spatial learning and memory tasks occurs at 3 wk of age in rodents. We reported that the developmental increase of spontaneous alternation in a Y-maze was related to changes in temporal dynamics of fast glutamatergic synaptic transmission in the hippocampus. We also showed that, during allothetic behaviors in the Y-maze, network oscillation power increased at frequency bands known to support spatial learning and memory in adults...
March 2018: Learning & Memory
https://www.readbyqxmd.com/read/29447844/angiotensin-ii-facilitates-gabaergic-neurotransmission-at-postsynaptic-sites-in-rat-amygdala-neurons
#4
Bo Hu, Hu Qiao, Tian Cao, Bo Sun, Xiao Luo, Ru Jia, Yuanyuan Fan, Nan Wang, Yi Lu, Jianqun Yan
The central nucleus of the amygdala (CeA) is critical in the regulation of sodium appetite. Angiotensin II (Ang II) is important in the generation of sodium appetite and may function as a neurotransmitter or modulator to affect the synaptic transmission and the excitability of neurons. However, the role of Ang II in the CeA remains unclear. In this study, we determined the effects of Ang II on the excitatory and inhibitory synaptic inputs to the CeA neurons in brain slices with whole-cell patch-clamp recordings...
February 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29447486/the-development-of-mid-wavelength-photoresponsivity-in-the-mouse-retina
#5
Paul J Bonezzi, Maureen E Stabio, Jordan M Renna
PURPOSE: Photoreceptors in the mouse retina express much of the molecular machinery necessary for phototransduction and glutamatergic transmission prior to eye opening at postnatal day 13 (P13). Light responses have been observed collectively from rod and cone photoreceptors via electroretinogram recordings as early as P13 in mouse, and the responses are known to become more robust with maturation, reaching a mature state by P30. Photocurrents from single rod outer segments have been recorded at P12, but no earlier, and similar studies on cone photoreceptors have been done, but only in the adult mouse retina...
February 15, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29445765/-in-vivo-observation-of-structural-changes-in-neocortical-catecholaminergic-projections-in-response-to-drugs-of-abuse
#6
Mai M Morimoto, Shinji Tanaka, Shunsuke Mizutani, Shinji Urata, Kazuto Kobayashi, Shigeo Okabe
Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an important role in cognitive functions and dysfunctions including learning, addiction, and mental disorders. While dynamics of glutamatergic synapses have been well studied in such contexts, little is known regarding catecholaminergic projections, owing to lack of robust methods. Here we report a system to monitor catecholaminergic projections in vivo over the timeframes that such events occur. Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase promoter in a transgenic mouse line enabled us to perform two-photon imaging of cortical catecholaminergic projections through a cranial window...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29444988/nmda-type-glutamate-receptor-activation-promotes-vascular-remodeling-and-pulmonary-arterial-hypertension
#7
Sébastien J Dumas, Gilles Bru-Mercier, Audrey Courboulin, Marceau Quatredeniers, Catherine Rücker-Martin, Fabrice Antigny, Morad K Nakhleh, Benoit Ranchoux, Elodie Gouadon, Maria-Candida Vinhas, Matthieu Vocelle, Nicolas Raymond, Peter Dorfmüller, Elie Fadel, Frédéric Perros, Marc Humbert, Sylvia Cohen-Kaminsky
Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown...
February 14, 2018: Circulation
https://www.readbyqxmd.com/read/29444426/inferior-olive-hcn1-channels-coordinate-synaptic-integration-and-complex-spike-timing
#8
Derek L F Garden, Marlies Oostland, Marta Jelitai, Arianna Rinaldi, Ian Duguid, Matthew F Nolan
Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444252/human-striatal-response-to-reward-anticipation-linked-to-hippocampal-glutamate-levels
#9
Matthijs G Bossong, Robin Wilson, Elizabeth Appiah-Kusi, Philip McGuire, Sagnik Bhattacharyya
Background: Dysfunctional reward processing is associated with a number of psychiatric disorders, such as addiction and schizophrenia. It is thought that reward is regulated mainly by dopamine transmission in the ventral striatum. Contemporary animal models suggest that striatal dopamine concentrations and associated behaviours are related to glutamatergic functioning in the ventral hippocampus. However, in humans the association between reward-related ventral striatal response and hippocampal glutamate levels is unclear...
February 10, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29440309/the-phosphodiesterase-2a-inhibitor-tak-915-ameliorates-cognitive-impairments-and-social-withdrawal-in-n-methyl-d-aspartate-receptor-antagonist-induced-rat-models-of-schizophrenia
#10
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29439750/differential-neural-reward-mechanisms-in-treatment-responsive-and-treatment-resistant-schizophrenia
#11
Lucy D Vanes, Elias Mouchlianitis, Tracy Collier, Bruno B Averbeck, Sukhi S Shergill
BACKGROUND: The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients. METHODS: In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces...
February 14, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29438442/the-sirna-mediated-knockdown-of-glun3a-in-46c-derived-neural-stem-cells-affects-mrna-expression-levels-of-neural-genes-including-known-iglur-interactors
#12
Svenja Pachernegg, Sebastian Eilebrecht, Elke Eilebrecht, Hendrik Schöneborn, Sebastian Neumann, Arndt G Benecke, Michael Hollmann
For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages...
2018: PloS One
https://www.readbyqxmd.com/read/29437267/pharmacoproteomics-profile-in-response-to-acamprosate-treatment-of-an-alcoholism-animal-model
#13
Caroline E Germany, Ashlie N Reker, David J Hinton, Alfredo Oliveros, Xinggui Shen, Lindsey G Andres-Beck, Katheryn M Wininger, Marjan Trutchul, Urska Cvek, Doo-Sup Choi, Hyung W Nam
Acamprosate is an FDA-approved medication for the treatment of alcoholism that is unfortunately only effective in certain patients. Although acamprosate known to stabilize the hyper-glutamatergic state in alcoholism, pharmacological mechanisms of action in brain tissue remains unknown. To investigate the mechanism of acamprosate efficacy, we employed a pharmacoproteomics approach using an animal model of alcoholism, type 1 equilibrative nucleoside transporter (ENT1) null mice. Our results demonstrated that acamprosate treatment significantly decreased both ethanol drinking and preference in ENT1 null mice compared to that of wild-type mice...
February 13, 2018: Proteomics
https://www.readbyqxmd.com/read/29435486/transient-receptor-potential-channels-trpm4-and-trpc3-critically-contribute-to-respiratory-motor-pattern-formation-but-not-rhythmogenesis-in-rodent-brainstem-circuits
#14
Hidehiko Koizumi, Tibin T John, Justine X Chia, Mohammad F Tariq, Ryan S Phillips, Bryan Mosher, Yonghua Chen, Ryan Thompson, Ruli Zhang, Naohiro Koshiya, Jeffrey C Smith
Transient receptor potential channel, TRPM4, the putative molecular substrate for Ca2+-activated nonselective cation current (ICAN), is hypothesized to generate bursting activity of pre-Bötzinger complex (pre-BötC) inspiratory neurons and critically contribute to respiratory rhythmogenesis. Another TRP channel, TRPC3, which mediates Na+/Ca2+ fluxes, may be involved in regulating Ca2+-related signaling, including affecting TRPM4/ICAN in respiratory pre-BötC neurons. However, TRPM4 and TRPC3 expression in pre-BötC inspiratory neurons and functional roles of these channels remain to be determined...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29434572/stress-and-corticosteroids-aggravate-morphological-changes-in-the-dentate-gyrus-after-early-life-experimental-febrile-seizures-in-mice
#15
Jolien S van Campen, Ellen V S Hessel, Kirsten Bohmbach, Giorgio Rizzi, Paul J Lucassen, Sada Lakshmi Turimella, Eduardo H L Umeoka, Gideon F Meerhoff, Kees P J Braun, Pierre N E de Graan, Marian Joëls
Stress is the most frequently self-reported seizure precipitant in patients with epilepsy. Moreover, a relation between ear stress and epilepsy has been suggested. Although ear stress and stress hormones are known to influence seizure threshold in rodents, effects on the development of epilepsy (epileptogenesis) are still unclear. Therefore, we studied the consequences of ear corticosteroid exposure for epileptogenesis, under highly controlled conditions in an animal model. Experimental febrile seizures (eFS) were elicited in 10-day-old mice by warm-air induced hyperthermia, while a control group was exposed to a normothermic condition...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29434537/how-can-a-ketogenic-diet-improve-motor-function
#16
REVIEW
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
https://www.readbyqxmd.com/read/29434375/bidirectional-and-long-lasting-control-of-alcohol-seeking-behavior-by-corticostriatal-ltp-and-ltd
#17
Tengfei Ma, Yifeng Cheng, Emily Roltsch Hellard, Xuehua Wang, Jiayi Lu, Xinsheng Gao, Cathy C Y Huang, Xiao-Yan Wei, Jun-Yuan Ji, Jun Wang
Addiction is proposed to arise from alterations in synaptic strength via mechanisms of long-term potentiation (LTP) and depression (LTD). However, the causality between these synaptic processes and addictive behaviors is difficult to demonstrate. Here we report that LTP and LTD induction altered operant alcohol self-administration, a motivated drug-seeking behavior. We first induced LTP by pairing presynaptic glutamatergic stimulation with optogenetic postsynaptic depolarization in the dorsomedial striatum, a brain region known to control goal-directed behavior...
February 12, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29434188/dopamine-d2-receptor-mediated-neuroprotection-in-a-g2019s-lrrk2-genetic-model-of-parkinson-s-disease
#18
Alessandro Tozzi, Michela Tantucci, Saverio Marchi, Petra Mazzocchetti, Michele Morari, Paolo Pinton, Andrea Mancini, Paolo Calabresi
Parkinson's disease (PD) is a neurodegenerative disorder in which genetic and environmental factors synergistically lead to loss of midbrain dopamine (DA) neurons. Mutation of leucine-rich repeated kinase2 (Lrrk2) genes is responsible for the majority of inherited familial cases of PD and can also be found in sporadic cases. The pathophysiological role of this kinase has to be fully understood yet. Hyperactivation of Lrrk2 kinase domain might represent a predisposing factor for both enhanced striatal glutamatergic release and mitochondrial vulnerability to environmental factors that are observed in PD...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29433094/fingolimod-reduces-the-clinical-expression-of-active-demyelinating-lesions-in-ms
#19
Signoriello Elisabetta, Landi Doriana, Monteleone Fabrizia, Saccà Francesco, Nicoletti Carolina Gabri, Buttari Fabio, Sica Francesco, Marfia Girolama Alessandra, Di Iorio Giuseppe, Lus Giacomo, Centonze Diego
BACKGROUND: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a...
February 5, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29432701/plasticity-of-light-induced-concurrent-glutamatergic-and-gabaergic-quantal-events-in-the-suprachiasmatic-nucleus
#20
Juan Cheng, Xu Huang, Yue Liang, Tian Xue, Liecheng Wang, Jin Bao
Neurons in the suprachiasmatic nucleus (SCN) exhibit circadian variation in their neuronal activities. Here, we show that their input synapses undergo daily regulation. We discovered daily variation in the frequencies, but not the peak amplitudes, of miniature postsynaptic currents (mPSCs) for both glutamatergic and GABAergic synapses. In addition, the changes in the frequencies of mPSCs from glutamatergic and GABAergic synapses were antiphasic: An increase in the glutamatergic mPSC frequency and a decrease in the GABAergic mPSC frequency co-occurred during the dark phase of the light-dark cycle...
February 2018: Journal of Biological Rhythms
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