Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 40, Issue 8, Pages 1260-1267Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b17-00131
Keywords
ketamine; depression; inflammation; toll-like receptor type 4 (TLR4); P2X7
Categories
Funding
- project of Hunan Provincial Health Bureau [C2013-008]
- University of South China [2013XQD22]
- Zhengxiang Scholar Program of the University of South China
- construct program of the key discipline in Hunan province
Ask authors/readers for more resources
The purpose of the present study was to investigate whether ketamine's rapid antidepressant effects were associated with its anti-inflammatory actions and to explore the underlying molecular mechanism. Depressive-like behaviors was induced in mice using chronic restraint stress (CRS) method. Anti-depressive effects of ketamine were evaluated by forced swimming tests (FST) and sucrose preference test (SPT). Subsequently, brain tissue was harvested to investigate inflammatory response in the hippocampus via investigating reactive microglia numbers, serum cytokines levels and the toll-like receptor type 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) pathway. CRS exposure caused depressive-like behaviors in mice, which was associated with increased pre-inflammatory cytokines (interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and IL-6) levels, reactive microglia numbers and up-regulated regulatory molecules such as TLR4/p38 and P2X7 receptor in hippocampus. Such neurobehavioral and biochemical abnormalities were normalized by ketamine treatment. CRS-induced depression-like behaviours are associated with activation of hippocampal inflammatory response, whereas down-regulation of pro-inflammatory cytokines may contribute to ketamine's antidepressant effects in mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available