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Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress
Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605528/ https://www.ncbi.nlm.nih.gov/pubmed/28928398 http://dx.doi.org/10.1038/s41598-017-12183-z |
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author | Hu, Die Yu, Zhou-Long Zhang, Yan Han, Ying Zhang, Wen Lu, Lin Shi, Jie |
author_facet | Hu, Die Yu, Zhou-Long Zhang, Yan Han, Ying Zhang, Wen Lu, Lin Shi, Jie |
author_sort | Hu, Die |
collection | PubMed |
description | Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na(+)/K(+)/2Cl(−) cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K(+)/2Cl(−) cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABA(A)) receptor subunits on postnatal day 40 in the hippocampus. NKCC1 inhibition by the U.S. Food and Drug Administration-approved drug bumetanide during the first two postnatal weeks rescued the depressive- and anxiety-like behavior that was induced by maternal separation and decreased the expression of NKCC1, KCC2 and GABA(A) receptor α1 and β2,3 subunits in the hippocampus. Bumetanide treatment during early development did not adversely affect body weight or normal behaviors in naive rats, or affect serum osmolality in adult rats. These results suggest that bumetanide treatment during early development may prevent the maternal separation-induced susceptibility to stress and impairments in GABAergic transmission in the hippocampus. |
format | Online Article Text |
id | pubmed-5605528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56055282017-09-20 Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress Hu, Die Yu, Zhou-Long Zhang, Yan Han, Ying Zhang, Wen Lu, Lin Shi, Jie Sci Rep Article Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na(+)/K(+)/2Cl(−) cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K(+)/2Cl(−) cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABA(A)) receptor subunits on postnatal day 40 in the hippocampus. NKCC1 inhibition by the U.S. Food and Drug Administration-approved drug bumetanide during the first two postnatal weeks rescued the depressive- and anxiety-like behavior that was induced by maternal separation and decreased the expression of NKCC1, KCC2 and GABA(A) receptor α1 and β2,3 subunits in the hippocampus. Bumetanide treatment during early development did not adversely affect body weight or normal behaviors in naive rats, or affect serum osmolality in adult rats. These results suggest that bumetanide treatment during early development may prevent the maternal separation-induced susceptibility to stress and impairments in GABAergic transmission in the hippocampus. Nature Publishing Group UK 2017-09-19 /pmc/articles/PMC5605528/ /pubmed/28928398 http://dx.doi.org/10.1038/s41598-017-12183-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hu, Die Yu, Zhou-Long Zhang, Yan Han, Ying Zhang, Wen Lu, Lin Shi, Jie Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title | Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title_full | Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title_fullStr | Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title_full_unstemmed | Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title_short | Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
title_sort | bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605528/ https://www.ncbi.nlm.nih.gov/pubmed/28928398 http://dx.doi.org/10.1038/s41598-017-12183-z |
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