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Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress

A pertinent mechanism by which stress impacts learning and memory is through stress-induced plastic changes in glutamatergic transmission in the hippocampus. For instance, acute stress has been shown to alter the expression, binding, and function of the ionotropic glutamate N-methyl-D-aspartate rece...

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Autores principales: Tse, Yiu Chung, Nath, Moushumi, Larosa, Amanda, Wong, Tak Pan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531402/
https://www.ncbi.nlm.nih.gov/pubmed/34690693
http://dx.doi.org/10.3389/fnmol.2021.716675
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author Tse, Yiu Chung
Nath, Moushumi
Larosa, Amanda
Wong, Tak Pan
author_facet Tse, Yiu Chung
Nath, Moushumi
Larosa, Amanda
Wong, Tak Pan
author_sort Tse, Yiu Chung
collection PubMed
description A pertinent mechanism by which stress impacts learning and memory is through stress-induced plastic changes in glutamatergic transmission in the hippocampus. For instance, acute stress has been shown to alter the expression, binding, and function of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR). However, the consequences of chronic stress, which could lead to various stress-related brain disorders, on NMDAR function remain unclear. While most studies on NMDARs focused on these receptors in synapses (synaptic NMDARs or sNMDARs), emerging findings have revealed functional roles of NMDARs outside synapses (extrasynaptic NMDARs or exNMDARs) that are distinct from those of sNMDARs. Using a restraint stress paradigm in adult rats, the objective of the current study is to examine whether sNMDARs and exNMDARs in the hippocampus are differentially regulated by acute and chronic stress. We examined sNMDAR and exNMDAR function in dorsal CA1 hippocampal neurons from brain slices of adult rats that were acutely (1 episode) or chronically (21 daily episodes) stressed by restraint (30 min). We found that acute stress increases sNMDAR but suppresses exNMDAR function. Surprisingly, we only observed a reduction in exNMDAR function after chronic stress. Taken together, our findings suggest that sNMDARs and exNMDARs may be differentially regulated by acute and chronic stress. Most importantly, the observed suppression in exNMDAR function by both acute and chronic stress implies crucial but overlooked roles of hippocampal exNMDARs in stress-related disorders.
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spelling pubmed-85314022021-10-23 Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress Tse, Yiu Chung Nath, Moushumi Larosa, Amanda Wong, Tak Pan Front Mol Neurosci Neuroscience A pertinent mechanism by which stress impacts learning and memory is through stress-induced plastic changes in glutamatergic transmission in the hippocampus. For instance, acute stress has been shown to alter the expression, binding, and function of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR). However, the consequences of chronic stress, which could lead to various stress-related brain disorders, on NMDAR function remain unclear. While most studies on NMDARs focused on these receptors in synapses (synaptic NMDARs or sNMDARs), emerging findings have revealed functional roles of NMDARs outside synapses (extrasynaptic NMDARs or exNMDARs) that are distinct from those of sNMDARs. Using a restraint stress paradigm in adult rats, the objective of the current study is to examine whether sNMDARs and exNMDARs in the hippocampus are differentially regulated by acute and chronic stress. We examined sNMDAR and exNMDAR function in dorsal CA1 hippocampal neurons from brain slices of adult rats that were acutely (1 episode) or chronically (21 daily episodes) stressed by restraint (30 min). We found that acute stress increases sNMDAR but suppresses exNMDAR function. Surprisingly, we only observed a reduction in exNMDAR function after chronic stress. Taken together, our findings suggest that sNMDARs and exNMDARs may be differentially regulated by acute and chronic stress. Most importantly, the observed suppression in exNMDAR function by both acute and chronic stress implies crucial but overlooked roles of hippocampal exNMDARs in stress-related disorders. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531402/ /pubmed/34690693 http://dx.doi.org/10.3389/fnmol.2021.716675 Text en Copyright © 2021 Tse, Nath, Larosa and Wong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tse, Yiu Chung
Nath, Moushumi
Larosa, Amanda
Wong, Tak Pan
Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title_full Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title_fullStr Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title_full_unstemmed Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title_short Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
title_sort opposing changes in synaptic and extrasynaptic n-methyl-d-aspartate receptor function in response to acute and chronic restraint stress
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531402/
https://www.ncbi.nlm.nih.gov/pubmed/34690693
http://dx.doi.org/10.3389/fnmol.2021.716675
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