G-1 exhibit antidepressant effect, increase of hippocampal ERs expression and improve hippocampal redox status in aged female rats.
Aging
/ drug effects
Animals
Cyclopentanes
/ pharmacology
Disease Models, Animal
Estrogens
/ blood
Exploratory Behavior
/ drug effects
Female
Gene Expression Regulation
/ drug effects
Hippocampus
/ drug effects
Maze Learning
/ drug effects
Membrane Potential, Mitochondrial
/ drug effects
Mitochondria
/ drug effects
Mood Disorders
/ drug therapy
Ovariectomy
Oxidation-Reduction
/ drug effects
Oxidative Stress
/ drug effects
Quinolines
/ pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Estrogen
/ metabolism
Superoxide Dismutase
/ metabolism
Swimming
/ psychology
Depression
Estrogen receptors
GPER
Mitochondrial protection
Oestradiol
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
22
04
2018
revised:
09
07
2018
accepted:
20
07
2018
pubmed:
25
7
2018
medline:
4
4
2019
entrez:
25
7
2018
Statut:
ppublish
Résumé
Postmenopausal depression has been shown to be related to the reduction of ovarian hormones produced as a woman transitions from a menopausal to a post-menopausal stage. What remains to be known is which type of estrogen receptor plays a key role in estrogen neuroprotection, a process that may be mediated by potentiating brain mitochondrial function and inhibiting mitochondria-associated apoptosis. In order to better imitate the condition of postmenopause, we conducted our research on aged female rats. Plasma estrogen levels declined significantly in ovariectomized rats and 16-month-old female rats, while anxiety and depression-like behavior increase. Moreover, ERα, ERβ, GPER, Bcl2 and UCP2 expression decreased significantly in hippocampus in female rats following ovariectomy. In our study, the anxiety and depression-like behavior in aged female rats were significantly relieved after the treatment of G-1, the GPER agonist. Furthermore, G-1 could reverse the reduction of ERα, ERβ, GPER, Bcl2 and UCP2 expression within the hippocampus. Mitochondrial JC-1 staining indicated that mitochondrial membrane potential increased after G-1 treatment. In addition, total antioxidant capacity (TAC) and superoxide dismutase activity (SOD) were found to be elevated in aged female rats following G-1 treatment. Taken together, estrogen receptors, especially GPER, may activate anti-apoptotic signaling and accelerate mitochondrial function. Therefore, GPER could be the potential therapeutic target for estrogen deficiency-related affective disorders.
Identifiants
pubmed: 30041006
pii: S0166-4328(18)30575-8
doi: 10.1016/j.bbr.2018.07.017
pii:
doi:
Substances chimiques
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
0
Cyclopentanes
0
Estrogens
0
Quinolines
0
Receptors, Estrogen
0
Superoxide Dismutase
EC 1.15.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
845-852Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.