Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Bibliographic Details
Title: Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus
Authors: Ying Yin, Shiyu Qian, Yifan Chen, Yan Sun, Yuqiao Li, Yongfei Yu, Jianqing Li, Zhangjie Wu, Xinlang Yu, Rui Ge, Jia Han, Dongdong Sun, Haoxin Wu, Lanying Liu, Wenda Xue, Wei Wang
Source: Frontiers in Behavioral Neuroscience, Vol 15 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
Subject Terms: sex difference, YG, nNOS, CaMKII, CREB, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
More Details: Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1662-5153
Relation: https://www.frontiersin.org/articles/10.3389/fnbeh.2021.640258/full; https://doaj.org/toc/1662-5153
DOI: 10.3389/fnbeh.2021.640258
Access URL: https://doaj.org/article/03a658a325684403977e78cf780e474f
Accession Number: edsdoj.03a658a325684403977e78cf780e474f
Database: Directory of Open Access Journals
More Details
ISSN:16625153
DOI:10.3389/fnbeh.2021.640258
Published in:Frontiers in Behavioral Neuroscience
Language:English