Cargando…
miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF
Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921013/ https://www.ncbi.nlm.nih.gov/pubmed/33718536 http://dx.doi.org/10.1016/j.ynstr.2021.100311 |
_version_ | 1783658387455606784 |
---|---|
author | Tong, Lei Li, Ming-Da Nie, Peng-Yin Chen, Yao Chen, Yu-Lu Ji, Li-Li |
author_facet | Tong, Lei Li, Ming-Da Nie, Peng-Yin Chen, Yao Chen, Yu-Lu Ji, Li-Li |
author_sort | Tong, Lei |
collection | PubMed |
description | Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF and is regulated by miR-132-3p. In the present study, we explored the possible molecular mechanism of miR-132, focusing on the involvement of MeCP2 and BDNF in the formation of anxiety-like symptoms of PTSD. Single prolonged stress (SPS) was used to establish a model of PTSD in adult rats and the anxiety-like behavior was tested by the elevated plus-maze (EPM). The level of miR-132 in the prefrontal cortex (PFC) was increased and intraventricular injection of anti-miR-132 could significantly improve the anxiety-like behavior of rats exposed to SPS through MeCP2 and the subsequent upregulation of BDNF levels. Then tropomyosin-related kinase B (TrkB) and downstream signals, including MAP kinase ERK1/2 and phosphoinositol 3-kinase (PI3K)/Akt pathways, were activated by BDNF upregulation, and might participate in regulating dendritic complexity and the expression of postsynaptic density-95 (PSD95) and synapsin I in the PFC of SPS rats. Furthermore, we found that the apoptosis of cells in PFC induced by SPS procedure could be alleviated by miR-132 inhibition. Our results suggest that miR-132 might be involved in the formation of anxiety-like symptoms of adult rat PTSD models by targeting MeCP2, and this effect is related to BDNF/TrkB and its downstream ERK and Akt signaling pathways. |
format | Online Article Text |
id | pubmed-7921013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-79210132021-03-12 miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF Tong, Lei Li, Ming-Da Nie, Peng-Yin Chen, Yao Chen, Yu-Lu Ji, Li-Li Neurobiol Stress Original Research Article Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF and is regulated by miR-132-3p. In the present study, we explored the possible molecular mechanism of miR-132, focusing on the involvement of MeCP2 and BDNF in the formation of anxiety-like symptoms of PTSD. Single prolonged stress (SPS) was used to establish a model of PTSD in adult rats and the anxiety-like behavior was tested by the elevated plus-maze (EPM). The level of miR-132 in the prefrontal cortex (PFC) was increased and intraventricular injection of anti-miR-132 could significantly improve the anxiety-like behavior of rats exposed to SPS through MeCP2 and the subsequent upregulation of BDNF levels. Then tropomyosin-related kinase B (TrkB) and downstream signals, including MAP kinase ERK1/2 and phosphoinositol 3-kinase (PI3K)/Akt pathways, were activated by BDNF upregulation, and might participate in regulating dendritic complexity and the expression of postsynaptic density-95 (PSD95) and synapsin I in the PFC of SPS rats. Furthermore, we found that the apoptosis of cells in PFC induced by SPS procedure could be alleviated by miR-132 inhibition. Our results suggest that miR-132 might be involved in the formation of anxiety-like symptoms of adult rat PTSD models by targeting MeCP2, and this effect is related to BDNF/TrkB and its downstream ERK and Akt signaling pathways. Elsevier 2021-02-25 /pmc/articles/PMC7921013/ /pubmed/33718536 http://dx.doi.org/10.1016/j.ynstr.2021.100311 Text en © 2021 The Authors. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Article Tong, Lei Li, Ming-Da Nie, Peng-Yin Chen, Yao Chen, Yu-Lu Ji, Li-Li miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title | miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title_full | miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title_fullStr | miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title_full_unstemmed | miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title_short | miR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF |
title_sort | mir-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in pfc, and upregulates the expression of mecp2 and bdnf |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921013/ https://www.ncbi.nlm.nih.gov/pubmed/33718536 http://dx.doi.org/10.1016/j.ynstr.2021.100311 |
work_keys_str_mv | AT tonglei mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf AT limingda mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf AT niepengyin mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf AT chenyao mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf AT chenyulu mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf AT jilili mir132downregulationalleviatesbehavioralimpairmentofratsexposedtosingleprolongedstressreducesthelevelofapoptosisinpfcandupregulatestheexpressionofmecp2andbdnf |