PMID- 31781286
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1741-427X (Print)
IS  - 1741-4288 (Electronic)
IS  - 1741-427X (Linking)
VI  - 2019
DP  - 2019
TI  - Antidepressive Effects of Kamishoyosan through 5-HT1AReceptor and PKA-CREB-BDNF 
      Signaling in the Hippocampus in Postmenopausal Depression-Model Mice.
PG  - 9475384
LID - 10.1155/2019/9475384 [doi]
LID - 9475384
AB  - Females are well known to suffer disproportionately more than males from 
      stress-related neuropsychiatric disorders, especially during perimenopausal and 
      postmenopausal periods. In addition to a decline in serum estradiol levels, 
      environmental stress and social stress likely contribute to the development of 
      neuropsychiatric symptoms in perimenopausal and postmenopausal women. 
      Kamishoyosan (KSS) is a traditional Japanese Kampo medicine, composed of a 
      specified mixture of 10 crude compounds derived from plant sources, widely used 
      for various neuropsychiatric symptoms in perimenopausal and postmenopausal women. 
      However, the molecular mechanisms underlying KSS-mediated attenuation of 
      neuropsychological symptoms and stress-response behaviors in perimenopausal and 
      postmenopausal women remain unknown. In the present study, we first established a 
      mouse model for postmenopausal depression-like signs using chronic 
      water-immersion and restraint-stressed ovariectomized (OVX) mice to investigate 
      the underlying molecular mechanism of KSS. We found that continuous 
      administration of KSS to these mice normalized the activation of the 
      hypothalamic-pituitary-adrenal (HPA) axis, ameliorated stress-induced depressive 
      behavior, and prevented a decrease of neurogenesis in the hippocampus. As 
      previous studies have implicated dysfunction of the hippocampal 5-HT1A receptor 
      (5-HT1AR) in depressive disorders, we also evaluated the effect of KSS on 5-HT1AR 
      expression and the protein kinase A- (PKA-) cAMP response element-binding- 
      (CREB-) brain-derived neurotrophic factor (BDNF) signaling pathway in the 
      hippocampus in this model. The level of 5-HT1AR in the hippocampus decreased in 
      chronic stress-exposed OVX mice, while KSS treatment normalized the 
      stress-induced decrease in 5-HT1AR expression in the hippocampus of chronic 
      stress-exposed OVX mice. Furthermore, we found that KSS treatment upregulated the 
      expression levels of phosphorylated PKA (p-PKA), phosphorylated CREB (p-CREB), 
      and BDNF in the hippocampus in chronic stress-exposed OVX mice. These results 
      suggest that KSS improves neuropsychiatric symptoms through 5-HT1AR and 
      PKA-CREB-BDNF signaling in the hippocampus in postmenopausal women.
CI  - Copyright (c) 2019 Shoko Shimizu et al.
FAU - Shimizu, Shoko
AU  - Shimizu S
AUID- ORCID: 0000-0001-6524-3888
AD  - Division of Molecular Brain Science, Research Institute of Traditional Asian 
      Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
FAU - Ishino, Yugo
AU  - Ishino Y
AD  - Division of Molecular Brain Science, Research Institute of Traditional Asian 
      Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
FAU - Takeda, Takashi
AU  - Takeda T
AUID- ORCID: 0000-0003-2428-1946
AD  - Division of Women Medicine, Research Institute of Traditional Asian Medicine, 
      Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
FAU - Tohyama, Masaya
AU  - Tohyama M
AD  - Division of Molecular Brain Science, Research Institute of Traditional Asian 
      Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
AD  - Osaka Prefectural Hospital Organization, Osaka, Osaka 541-8567, Japan.
FAU - Miyata, Shingo
AU  - Miyata S
AUID- ORCID: 0000-0001-8064-070X
AD  - Division of Molecular Brain Science, Research Institute of Traditional Asian 
      Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
LA  - eng
PT  - Journal Article
DEP - 20191103
PL  - United States
TA  - Evid Based Complement Alternat Med
JT  - Evidence-based complementary and alternative medicine : eCAM
JID - 101215021
PMC - PMC6874869
COIS- The authors declare that there are no conflicts of interest regarding the 
      publication of this article.
EDAT- 2019/11/30 06:00
MHDA- 2019/11/30 06:01
PMCR- 2019/11/03
CRDT- 2019/11/30 06:00
PHST- 2019/05/18 00:00 [received]
PHST- 2019/09/27 00:00 [revised]
PHST- 2019/10/14 00:00 [accepted]
PHST- 2019/11/30 06:00 [entrez]
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2019/11/30 06:01 [medline]
PHST- 2019/11/03 00:00 [pmc-release]
AID - 10.1155/2019/9475384 [doi]
PST - epublish
SO  - Evid Based Complement Alternat Med. 2019 Nov 3;2019:9475384. doi: 
      10.1155/2019/9475384. eCollection 2019.