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Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior
Early-life stress (ELS) predisposes individuals to psychiatric disorders, including anxiety and depression, and cognitive impairments later in life. However, the underlying molecular mechanisms are not completely understood. Developmental deficits in hippocampal synaptic plasticity are among the pri...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767996/ https://www.ncbi.nlm.nih.gov/pubmed/33381149 http://dx.doi.org/10.3389/fgene.2020.590068 |
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author | Wang, Anfeng Zou, Xiaojuan Wu, Jiajia Ma, Qingyu Yuan, Naijun Ding, Fengmin Li, Xiaojuan Chen, Jiaxu |
author_facet | Wang, Anfeng Zou, Xiaojuan Wu, Jiajia Ma, Qingyu Yuan, Naijun Ding, Fengmin Li, Xiaojuan Chen, Jiaxu |
author_sort | Wang, Anfeng |
collection | PubMed |
description | Early-life stress (ELS) predisposes individuals to psychiatric disorders, including anxiety and depression, and cognitive impairments later in life. However, the underlying molecular mechanisms are not completely understood. Developmental deficits in hippocampal synaptic plasticity are among the primary detrimental alterations in brain function induced by ELS. Impaired synaptic plasticity is usually accompanied by decreased synaptic proteins, such as postsynaptic density 95 (PSD95) and synaptophysin, which are important for synaptic function. The mTOR signaling pathway plays a vital role in regulating protein translation, and mTOR activation is functionally associated with synaptic protein synthesis. In the present study, we observed whether ELS impacts synaptic protein synthesis and mTOR signaling, which is involved in synaptic plasticity. Herein, we established a maternal separation (MS) and chronic restraint stress (CRS) model and evaluated anxiety-like behavior and cognitive function (e.g., learning and memory) in adulthood through behavioral examination and analyzed hippocampal expression levels of PSD95 and synaptophysin. To explore whether the mTOR signaling pathway was associated with ELS, we also examined the activity of mTOR and s6. The behavior tests indicated that maternally separated mice showed increased anxiety-like behavior and cognitive impairments. PSD95 and synaptophysin mRNA and protein expression levels were decreased in the hippocampus, and phosphorylated mTOR and phosphorylated s6 were significantly decreased in maternally separated mice vs. those not exposed to MS. Our data demonstrate that MS impairs synaptic plasticity and inhibits mTOR signaling, specifically via s6. Therefore, we speculate that ELS decreased synaptic plasticity via the inhibition of the mTOR pathway in the hippocampus, which may underlie vulnerability to stress and mental disorders in adulthood. |
format | Online Article Text |
id | pubmed-7767996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77679962020-12-29 Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior Wang, Anfeng Zou, Xiaojuan Wu, Jiajia Ma, Qingyu Yuan, Naijun Ding, Fengmin Li, Xiaojuan Chen, Jiaxu Front Genet Genetics Early-life stress (ELS) predisposes individuals to psychiatric disorders, including anxiety and depression, and cognitive impairments later in life. However, the underlying molecular mechanisms are not completely understood. Developmental deficits in hippocampal synaptic plasticity are among the primary detrimental alterations in brain function induced by ELS. Impaired synaptic plasticity is usually accompanied by decreased synaptic proteins, such as postsynaptic density 95 (PSD95) and synaptophysin, which are important for synaptic function. The mTOR signaling pathway plays a vital role in regulating protein translation, and mTOR activation is functionally associated with synaptic protein synthesis. In the present study, we observed whether ELS impacts synaptic protein synthesis and mTOR signaling, which is involved in synaptic plasticity. Herein, we established a maternal separation (MS) and chronic restraint stress (CRS) model and evaluated anxiety-like behavior and cognitive function (e.g., learning and memory) in adulthood through behavioral examination and analyzed hippocampal expression levels of PSD95 and synaptophysin. To explore whether the mTOR signaling pathway was associated with ELS, we also examined the activity of mTOR and s6. The behavior tests indicated that maternally separated mice showed increased anxiety-like behavior and cognitive impairments. PSD95 and synaptophysin mRNA and protein expression levels were decreased in the hippocampus, and phosphorylated mTOR and phosphorylated s6 were significantly decreased in maternally separated mice vs. those not exposed to MS. Our data demonstrate that MS impairs synaptic plasticity and inhibits mTOR signaling, specifically via s6. Therefore, we speculate that ELS decreased synaptic plasticity via the inhibition of the mTOR pathway in the hippocampus, which may underlie vulnerability to stress and mental disorders in adulthood. Frontiers Media S.A. 2020-12-14 /pmc/articles/PMC7767996/ /pubmed/33381149 http://dx.doi.org/10.3389/fgene.2020.590068 Text en Copyright © 2020 Wang, Zou, Wu, Ma, Yuan, Ding, Li and Chen. http://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 | Genetics Wang, Anfeng Zou, Xiaojuan Wu, Jiajia Ma, Qingyu Yuan, Naijun Ding, Fengmin Li, Xiaojuan Chen, Jiaxu Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title | Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title_full | Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title_fullStr | Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title_full_unstemmed | Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title_short | Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior |
title_sort | early-life stress alters synaptic plasticity and mtor signaling: correlation with anxiety-like and cognition-related behavior |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767996/ https://www.ncbi.nlm.nih.gov/pubmed/33381149 http://dx.doi.org/10.3389/fgene.2020.590068 |
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