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Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress

It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic anti...

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Autores principales: Zhang, Shanshan, Hu, Juntao, Liu, Guixue, Wu, Haoran, Li, Meihui, Shi, Chenye, Liu, Qiong, Li, Wensheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187713/
https://www.ncbi.nlm.nih.gov/pubmed/35688836
http://dx.doi.org/10.1038/s41398-022-02006-9
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author Zhang, Shanshan
Hu, Juntao
Liu, Guixue
Wu, Haoran
Li, Meihui
Shi, Chenye
Liu, Qiong
Li, Wensheng
author_facet Zhang, Shanshan
Hu, Juntao
Liu, Guixue
Wu, Haoran
Li, Meihui
Shi, Chenye
Liu, Qiong
Li, Wensheng
author_sort Zhang, Shanshan
collection PubMed
description It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic antidepressant, clomipramine. We designed a series of experiments to find its role in depressive-like behavior, hippocampal neuroinflammation as well as hippocampal volume changes induced by chronic unpredictable mild stress (CMS). Rats exhibited defective behavior and hippocampal neuroinflammation after 12 weeks of CMS, which included elevated expression of cleaved interleukin-1β (IL-1β) and NLRP3 inflammasome together with the activation of microglia. Rats exposed to CMS showed weakened behavioral defects, reduced expression of IL-18, IL-6, and IL-1β along with reversed activation of microglia after clomipramine treatment. This indicates that the antidepressant effect of clomipramine may be related to the reduced expression of NLRP3 inflammasome and cleaved IL-1β. Moreover, we found an increased hippocampal volume in rats exposed to CMS after clomipramine treatment while CMS failed to affect hippocampal volume. All these results indicate that the NLRP3 inflammasome of microglia in the hippocampus is related to the antidepressant effects of clomipramine and CMS-induced depressive-like behavior in rats.
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spelling pubmed-91877132022-06-12 Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress Zhang, Shanshan Hu, Juntao Liu, Guixue Wu, Haoran Li, Meihui Shi, Chenye Liu, Qiong Li, Wensheng Transl Psychiatry Article It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic antidepressant, clomipramine. We designed a series of experiments to find its role in depressive-like behavior, hippocampal neuroinflammation as well as hippocampal volume changes induced by chronic unpredictable mild stress (CMS). Rats exhibited defective behavior and hippocampal neuroinflammation after 12 weeks of CMS, which included elevated expression of cleaved interleukin-1β (IL-1β) and NLRP3 inflammasome together with the activation of microglia. Rats exposed to CMS showed weakened behavioral defects, reduced expression of IL-18, IL-6, and IL-1β along with reversed activation of microglia after clomipramine treatment. This indicates that the antidepressant effect of clomipramine may be related to the reduced expression of NLRP3 inflammasome and cleaved IL-1β. Moreover, we found an increased hippocampal volume in rats exposed to CMS after clomipramine treatment while CMS failed to affect hippocampal volume. All these results indicate that the NLRP3 inflammasome of microglia in the hippocampus is related to the antidepressant effects of clomipramine and CMS-induced depressive-like behavior in rats. Nature Publishing Group UK 2022-06-10 /pmc/articles/PMC9187713/ /pubmed/35688836 http://dx.doi.org/10.1038/s41398-022-02006-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Shanshan
Hu, Juntao
Liu, Guixue
Wu, Haoran
Li, Meihui
Shi, Chenye
Liu, Qiong
Li, Wensheng
Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title_full Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title_fullStr Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title_full_unstemmed Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title_short Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
title_sort chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187713/
https://www.ncbi.nlm.nih.gov/pubmed/35688836
http://dx.doi.org/10.1038/s41398-022-02006-9
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