Clomipramine treatment reversed the glial pathology in a chronic unpredictable stress-induced rat model of depression.
Growing evidence indicates that glia pathology contributes to the pathophysiology and possibly the etiology of depression. The study investigates changes in behaviors and glial fibrillary associated protein (GFAP) in the rat hippocampus after chronic unpredictable stress (CUS), a rat model of depression. Furthermore, we studied the effects of clomipramine, one of tricyclic antidepressants (TCAs), known to modulate serotonin and norepinephrine uptake, on CUS-induced depressive-like behaviors and GFAP levels. Rats exposed to CUS showed behavioral deficits in physical state, open field test and forced swimming test and exhibited a significant decrease in GFAP expression in the hippocampus. Interestingly, the behavioral and GFAP expression changes induced by CUS were reversed by chronic treatment with the antidepressant clomipramine. The beneficial effects of clomipramine treatment on CUS-induced depressive-like behavior and GFAP expression provide further validation of our hypothesis that glial dysfunction contributes to the pathophysiology of depression and that glial elements may represent viable targets for new antidepressant drug development.
Liu
Qiong
Q
Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institutes of Brain Science, Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Li
Bing
B
Zhu
Hai-Yan
HY
Wang
Yan-Qing
YQ
Yu
Jin
J
Wu
Gen-Cheng
GC
D000818:Animals; D002997:Clomipramine / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D046352:Freezing Reaction, Cataleptic; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming
D002997:Clomipramine; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors