Stimulation of astrocytic sigma-1 receptor is sufficient to ameliorate inflammation- induced depression

Astrocytes play important roles in the development of depression. As a promising target for antidepressant development, sigma-1 receptor (Sig-1R) is reported to promote activation of astrocyte in chronic stress-induced depression in our previous study. However, astrocytes are hyper-activated in infl...

Full description

Saved in:
Bibliographic Details
Published in:Behavioural brain research 2021-07, Vol.410, p.113344, Article 113344
Main Authors: Guo, Lin, Gao, Tianyu, Gao, Ce, Jia, Xiaoxia, Ni, Jing, Han, Chaojun, Wang, Yun
Format: Article
Language:English
Subjects:
Activated astrocyte
Animals
Astrocytes - metabolism
Behavior, Animal - physiology
Cells, Cultured
Depression
Depression - etiology
Depression - metabolism
Depression - physiopathology
Disease Models, Animal
Inflammation - chemically induced
Inflammation - complications
Lipopolysaccharide
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
Receptors, sigma - metabolism
Sigma-1 Receptor
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Astrocytes play important roles in the development of depression. As a promising target for antidepressant development, sigma-1 receptor (Sig-1R) is reported to promote activation of astrocyte in chronic stress-induced depression in our previous study. However, astrocytes are hyper-activated in inflammation-induced depression, raising concerns of whether stimulation of astrocytic Sig-1R would exert antidepressant-like effect in inflammation-induced depression. Here we reported that specific stimulation of astrocytic Sig-1R using adeno-associated virus (AAV) significantly attenuated lipopolysaccharide (LPS)- induced depressive-like behavior in the forced swim test (FST), tail suspension test (TST), sucrose preference test, and improved the memory function in novel object recognition test. Besides, specific stimulation of astrocytic Sig-1R decreased the activation of astrocyte and microglia, as well as increased brain-derived neurotrophic factor (BDNF) in LPS-induced depression. In primary cultured astrocytes, overexpression of Sig-1R also reduced the expression of IL-1β, TNF-α, iNOS during inflammation-treated astrocyte. Taken together, the results suggest that specific stimulation of astrocytic Sig-1R ameliorates inflammation-induced depressive-like behavior, providing the evidence that astrocytic Sig-1R could represent a reliable therapeutic target for depression.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2021.113344