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https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#1
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29767953/pharmacological-and-electrophysiological-characterization-of-novel-nmda-receptor-antagonists
#2
Rosana Leiva, Matthew B Phillips, Andreea Larisa Turcu, Esther Gratacòs-Batlle, Lara León-García, Francesc X Sureda, David Soto, Jon W Johnson, Santiago Vazquez
This work reports the synthesis, and pharmacological and electrophysiological evaluation of new N-methyl-D-aspartic acid receptor (NMDAR) channel blocking antagonists featuring polycyclic scaffolds. Changes in the chemical structure modulate the potency and voltage dependence of inhibition. Two of the new antagonists display properties comparable to those of memantine, a clinically approved NMDAR antagonist.
May 16, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29766040/the-midline-axon-crossing-decision-is-regulated-through-an-activity-dependent-mechanism-by-the-nmda-receptor
#3
Jingxia Gao, Tamara J Stevenson, Adam D Douglass, Joshua P Barrios, Joshua L Bonkowsky
Axon guidance in vertebrates is controlled by genetic cascades as well as by intrinsic activity-dependent refinement of connections. Midline axon crossing is one of the best studied pathfinding models and is fundamental to the establishment of bilaterally symmetric nervous systems. However, it is not known whether crossing requires intrinsic activity in axons, and what controls that activity. Further, a mechanism linking neuronal activity and gene expression has not been identified for axon pathfinding. Using embryonic zebrafish, we found that the NMDA receptor (NMDAR) NR1...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29763637/neurosteroid-pregnenolone-sulfate-alone-and-as-augmentation-of-lurasidone-or-tandospirone-rescues-phencyclidine-induced-deficits-in-cognitive-function-and-social-interaction
#4
L Rajagopal, D Soni, H Y Meltzer
BACKGROUND: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA ) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A  R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients...
May 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29763633/estradiol-induced-enhancement-of-fear-extinction-in-female-rats-the-role-of-nmda-receptor-activation
#5
Bronwyn M Graham, Elliot Scott
Converging cross-species evidence indicates that fear extinction (the laboratory basis of exposure therapy for anxiety disorders) in females is modulated by endogenous and exogenous estradiol. The mechanisms underlying estradiol's influences on fear extinction are largely undefined. However, one likely candidate is the NMDA-receptor (NMDAr), activation of which is necessary for estradiol-mediated enhancements in structural and functional neural plasticity, as well as extinction consolidation in males. Here, we demonstrate that systemic co-administration of the non-competitive NMDAr antagonist, MK801, blocked the enhancement of fear extinction by systemic estradiol in ovariectomized rats...
May 12, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29749988/amelioration-of-pentylenetetrazole-induced-seizures-by-modulators-of-sigma-n-methyl-d-aspartate-and-ryanodine-receptors-in-mice
#6
Mojtaba Keshavarz, Behdad Yekzaman
Background: Sigma receptors, N-methyl-D-aspartate (NMDA) antagonist, and modulators of intracellular calcium may be useful for seizure control. Therefore, we aimed to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, against pentylenetetrazole (PTZ)-induced seizures in mice and assess ketamine and caffeine interaction with the antiepileptic effects of opipramol. Methods: PTZ (100 mg/kg) was used for the induction of seizure in 72 male albino Swiss strain of mice (n=8)...
March 2018: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29749444/effects-of-intravenous-anesthetics-on-the-phosphorylation-of-camp-response-element%C3%A2-binding-protein-in-hippocampal-slices-of-adult-mice
#7
Haiying Gao, Lingyu Zhang, Zhenyi Chen, Shuncui Liu, Qinghong Zhang, Bingxi Zhang
cAMP response‑element binding protein (CREB) functions in hippocampal synaptic plasticity and memory formation. However, it remains unknown whether intravenous anesthetics modulate CREB. The present study aimed to examine the effects of intravenous anesthetics on CREB phosphorylation in the mouse hippocampus. CREB phosphorylation was examined in hippocampal slices with and without pharmacological or intravenous anesthetics via immunoblotting. In a dose‑response experiment, the concentrations of intravenous anesthetics ranged from 10‑9 to 10‑4 mol/l for 1 h...
April 27, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748616/prion-protein-is-essential-for-the-re1-silencing-transcription-factor-rest-dependent-developmental-switch-in-synaptic-nmda-receptors
#8
Zhiqi Song, Wei Yang, Guangyu Cheng, Xiangmei Zhou, Lifeng Yang, Deming Zhao
It is important that the correct amounts of GluN2 subunits are maintained, as they determine NMDAR functional properties, which are crucial to neuronal communication, synaptogenesis and cognitive function. The transcriptional repressor RE1 silencing transcription factor (REST) is critical for the postnatal developmental switch in NMDARs. However, the mechanisms triggering REST and the link between NMDARs and REST are unclear. Here we show a new physiological essential role for cellular prion protein (PrPC ) in REST-dependent homeostasis and the developmental switch of NMDARs...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29741614/loss-of-cerebellar-glutamate-transporters-eaat4-and-glast-differentially-affects-the-spontaneous-firing-pattern-and-survival-of-purkinje-cells
#9
Emma M Perkins, Yvonne L Clarkson, Daumante Suminaite, Alastair R Lyndon, Kohichi Tanaka, Jeffrey D Rothstein, Paul Skehel, David J A Wyllie, Mandy Jackson
Loss of excitatory amino acid transporters (EAATs) has been implicated in a number of human diseases including spinocerebellar ataxias, Alzhiemer's disease and motor neuron disease. EAAT4 and GLAST/EAAT1 are the two predominant EAATs responsible for maintaining low extracellular glutamate levels and preventing neurotoxicity in the cerebellum, the brain region essential for motor control. Here using genetically modified mice we identify new critical roles for EAAT4 and GLAST/EAAT1 as modulators of Purkinje cell (PC) spontaneous firing patterns...
May 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29740359/profiling-of-amino-acids-and-their-derivatives-biogenic-amines-before-and-after-antipsychotic-treatment-in-first-episode-psychosis
#10
Liisa Leppik, Kärt Kriisa, Kati Koido, Kadri Koch, Kärolin Kajalaid, Liina Haring, Eero Vasar, Mihkel Zilmer
Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs)...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29737230/the-nitric-oxide-donor-sin-1-produced-panic-like-behaviour-and-fear-induced-antinociception-are-modulated-by-nmda-receptors-in-the-anterior-hypothalamus
#11
Luiz Luciano Falconi-Sobrinho, Norberto Cysne Coimbra
BACKGROUND: An excitatory imbalance in the hypothalamus of rodents caused by local chemical stimulation elicits fear-related defensive reactions such as escape and freezing. In addition, these panic attack-like defensive reactions induced by hypothalamic neurons may cause antinociception. However, there is a shortage of studies showing the participation of the anterior hypothalamic nucleus in these adaptive defensive mechanisms. Nitric oxide (NO) donors have been shown to evoke fear-related defensive responses when microinjected into paralimbic and limbic structures, and this excitatory neuromodulation can recruit the glutamatergic system...
April 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29735530/nmda-receptor-dependent-dephosphorylation-of-serine-387-in-argonaute-2-increases-its-degradation-and-affects-dendritic-spine-density-and-maturation
#12
Nicolas Paradis-Isler, Jannic Boehm
Argonaute (AGO) proteins are essential components of the microRNA (miRNA) pathway. AGO proteins are loaded with miRNAs to target mRNAs and thereby regulate mRNA stability and protein translation. As such, AGO proteins are important actors in controlling local protein synthesis, for instance, at dendritic spines and synapses. Although miRNA-mediated regulation of dendritic mRNAs has become a focus of intense interest over the past years, the mechanisms regulating neuronal AGO proteins remain largely unknown...
May 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29732929/drug-development-for-alzheimer-s-disease-review
#13
Kejing Lao, Naichun Ji, Xiaohua Zhang, Wenwei Qiao, Zhishu Tang, Xingchun Gou
Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is considered one of the most intractable medical problems with heavy social and economic costs. The current drugs for AD, including acetylcholinesterase inhibitors (AChEIs) and memantine, a NMDA receptor antagonist, only temporarily ameliorate cognitive decline, but are unable to stop or reverse the progression of dementia. This paper reviewed the recent advance in AD drug development. The drug discovery programs under clinical trials targeting cholinergic system, α7 nicotinic acetylcholine receptors (nAChRs), N-methyl-D-aspartate receptor (NMDAR), β-secretase, γ-secretase modulators, tau, inflammatory mediators and glucagon-like peptide-1 (GLP-1) were discussed...
May 7, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29723552/pi3k-akt-gsk3%C3%AE-induced-creb-activation-ameliorates-arsenic-mediated-alterations-in-nmda-receptors-and-associated-signaling-in-rat-hippocampus-neuroprotective-role-of-curcumin
#14
Pranay Srivastava, Yogesh K Dhuriya, Vivek Kumar, Akriti Srivastava, Richa Gupta, Rajendra K Shukla, Rajesh S Yadav, Hari N Dwivedi, Aditya B Pant, Vinay K Khanna
Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3 K/Akt/ GSK3β signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo - 20 mg/kg, body weight p.o. for 28 days; in vitro - 10 µM for 24 hrs) and curcumin (in vivo - 100 mg/kg body weight p.o. for 28 days; in vitro - 20 µM for 24 hrs) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro...
April 30, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29713269/effects-of-subanesthetic-ketamine-administration-on-visual-and-auditory-event-related-potentials-erp-in-humans-a-systematic-review
#15
André Schwertner, Maxciel Zortea, Felipe V Torres, Wolnei Caumo
Ketamine is a non-competitive N-Methyl-D-Aspartate (NMDA) receptor antagonist whose effect in subanesthetic doses has been studied for chronic pain and mood disorders treatment. It has been proposed that ketamine could change the perception of nociceptive stimuli by modulating the cortical connectivity and altering the top-down mechanisms that control conscious pain perception. As this is a strictly central effect, it would be relevant to provide fresh insight into ketamine's effect on cortical response to external stimuli...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29712923/activity-dependent-lona-regulates-translation-by-coordinating-rrna-transcription-and-methylation
#16
Dingfeng Li, Juan Zhang, Ming Wang, Xiaohui Li, Huarui Gong, Huiping Tang, Lin Chen, Lili Wan, Qiang Liu
The ribosome is indispensable for precisely controlling the capacity of protein synthesis. However, how translational machinery is coordinated to meet the translational demands remains elusive. Here, we identify a nucleolar-specific lncRNA (LoNA), its 5' portion binds and sequesters nucleolin to suppress rRNA transcription, and its snoRNA like 3' end recruits and diminishes fibrillarin activity to reduce rRNA methylation. Activity-dependent decrease of LoNA leads to elevated rRNA and ribosome levels, an increased proportion of polysomes, mRNA polysome loading, and protein translation...
April 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29712715/nmdar-dependent-argonaute-2-phosphorylation-regulates-mirna-activity-and-dendritic-spine-plasticity
#17
Dipen Rajgor, Thomas M Sanderson, Mascia Amici, Graham L Collingridge, Jonathan G Hanley
MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), underpinning a powerful mechanism for fine-tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins...
April 30, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29704590/protective-influences-of-n-acetylcysteine-against-alcohol-abstinence-induced-depression-by-regulating-biochemical-and-grin2a-grin2b-gene-expression-of-nmda-receptor-signaling-pathway-in-rats
#18
Rutuja Yawalkar, Harish Changotra, Girdhari Lal Gupta
Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake...
April 25, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29701047/-the-effects-of-electroacupuncture-at-shu-and-mu-points-of-stomach-on-gastric-motility-the-nmda-of-vagus-nerve-dorsal-nucleus-and-serum-no-expression-in-functional-dyspepsia-rats
#19
Liur Wang, Guoming Shen, Hao Wang, Mengjie Hu, Yongchuan Yao, Shu Ye
OBJECTIVE: To research the central molecular mechanism of gastric motility in functional dyspepsia (FD) rats treated with electroacupuncture (EA) at shu and mu points of stomach. METHODS: A total of 30 SD rats were randomized into a blank group, a model group, a Zhongwan+Weishu group, a Weishu group and a Zhongwan group, 6 rats in each group. FD rats were established by moderate clipping tail infuriation and irregular feeding except in the blank group. EA was used at "Zhongwan"(CV 12),"Weishu"(BL 21), and"Zhongwan"(CV 12) +"Weishu"(BL 21) in the corresponding groups for 7 days, once a day, and 20 min a time...
March 12, 2018: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29686261/synaptic-nanomodules-underlie-the-organization-and-plasticity-of-spine-synapses
#20
Martin Hruska, Nathan Henderson, Sylvain J Le Marchand, Haani Jafri, Matthew B Dalva
Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size...
May 2018: Nature Neuroscience
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