Wuling Capsule promotes hippocampal neurogenesis by improving expression of connexin 43 in rats exposed to chronic unpredictable mild stress.
OBJECTIVE
To investigate the effects of Wuling Capsule, a compound traditional Chinese herbal medicine, on hippocampal neurogenesis by examining the expressions of brain-derived neurotrophic factor (BDNF) and connexin 43 (Cx43) in rats with depression induced by chronic unpredictable mild stress (CMS), and thereby to explore its antidepressant mechanism.


METHODS
Forty-five adult male Sprague-Dawley rats were randomly divided into three groups: control group (n=15), untreated group (n=15) and Wuling group (n=15). All rats except those in the control group were subjected to 3-week CMS to induce depression. At the same time Wuling Capsule was daily added to the diet of the rats in the Wuling group at a dose of 100 mg/kg body weight for 21 days. The degree of depression was determined by sucrose preference test. BDNF expression and neurogenesis were tested by using immunohistochemical staining with BDNF and 5-bromodeoxyuridine (BrdU) antibodies; and the mRNA and protein expression levels of Cx43 in hippocampus were examined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting.


RESULTS
The numbers of BDNF-positive neurons and BrdU-positive particles in dentate gyrus (DG) were significantly decreased in CMS rats as compared with the normal rats, and the same changes were found in Cx43 mRNA and protein expressions. After Wuling Capsule treatment, the depressed behaviors were improved. Moreover, the reduced expression levels of Cx43 mRNA and protein and fewer newborn neurons induced by CMS were recovered to the normal levels. However, BDNF-positive cells remained low in DG.


CONCLUSIONS
Wuling Capsule can improve the low hippocampal neurogenesis in rats subjected to CMS and the antidepressant effects are related to enhancing the Cx43 expression but not through BDNF mediation.
Li
De-Qiang
DQ
Department of Neurology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Li
Xu-Juan
XJ
Duan
Jin-Feng
JF
Cai
Wei
W
D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological
D018031:Connexin 43; D004365:Drugs, Chinese Herbal; C533472:wuling