Mefenamic acid can attenuate depressive symptoms by suppressing microglia activation induced upon chronic stress.
Abstract
BACKGROUND:Depression is the most debilitating neuropsychiatric disorder, and psychosocial
stressors are major risk factors for the onset of depression. Depression is closely
associated with chronic inflammation and microglia are the principal mediators of
inflammation in the central nervous system (CNS). Mefenamic acid (MA) and celecoxib
are nonselective and selective inhibitors of cyclooxygenase (COX), respectively. COX
is a key enzyme in mediating inflammatory response in microglia. In this study, we
examine the effects of inhibiting COX by MA on depressive-like behaviors and microglia
activation in the hippocampus. METHODS:We evaluate the effect of MA on chronic mild
stress (CMS) induced depressive-like behavior by sucrose preference and forced swimming
tests. Effect of MA on microglia activation in dentate gyrus (DG) of hippocampus was
examined by immunohistochemistry. In vitro experiments including western blotting
and phagocytosis assay were used to investigate the effect of MA on microglia activation.
RESULTS:Behavioral assays reveal MA and celecoxib ameliorate CMS-induced depressive-like
behavior. Compared to the stressed mice, the number of activated/phagocytic microglia
(Iba1+/CD68+) in DG of hippocampus significantly decreases in stressed mice treated
with MA or celecoxib. MA and celecoxib play a role in inhibiting microglia activation
by inhibiting of ERK1/2 and P38 MAPK activation and iNOS expression. MA or celecoxib
also reduce the high phagocytic activity of activated microglia. CONCLUSION:MA inhibits
microglia activation/phagocytosis induced upon chronic stress in the hippocampus,
which might result in the improvement of depressive symptoms.
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https://hdl.handle.net/10161/21068Published Version (Please cite this version)
10.1016/j.brainres.2020.146846Publication Info
Feng, Xiaoye; Fan, Yang; & Chung, Chang Y (2020). Mefenamic acid can attenuate depressive symptoms by suppressing microglia activation
induced upon chronic stress. Brain research, 1740. pp. 146846. 10.1016/j.brainres.2020.146846. Retrieved from https://hdl.handle.net/10161/21068.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Chang Yong Chung
Professor of Biology at Duke Kunshan University

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