The effect of trans-resveratrol on post-stroke depression via regulation of hypothalamus-pituitary-adrenal axis.
Post-stroke depression (PSD) occurs about 40% among all stroke survivors, but the effective pharmacotherapy is inadequately understood. The present study investigated the effects of a natural polyphenol trans-resveratrol (RES) on behavioral changes after middle cerebral artery occlusion (MCAO) and examined what its molecular targets may be. RES was shown to decrease the infarct size and neurological scores after MCAO, suggesting the amelioration of brain damage and motor activity. RES also reversed the depressive-like behaviors 13 days after MCAO, both in the forced swimming and sucrose consumption tests. Moreover, MCAO-induced series abnormalities related to depressive-like behaviors, such as an abnormal adrenal gland weight to body weight ratio, an increased expression of the corticotropin-releasing factor (CRF) in the frontal cortex, hippocampus and hypothalamus, the differential expression of glucocorticoid receptor (GR) in these three brain regions, and a decreased brain-derived neurotrophic factor (BDNF) level, were ameliorated after treatment with increasing doses of RES at 10, 20 and 40 mg/kg via gavage. These findings provide compelling evidence that RES protects the brain against focal cerebral ischemia-induced injury, but most of all is its antidepressant-like effect on PSD, which might at least in part be mediated by regulation of hypothalamus-pituitary-adrenal axis function.
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China.
Cong
C
Pang
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China.
Liang
L
Cao
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325021, China.
Fan
F
Wu
Clinical Laboratory, Xuzhou No.1 People's Hospital, Xuzhou, Jiangsu Province, 221002, China.
Li
L
Wang
Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, 310006, China.
Gang
G
Wang
Wenzhou Third People's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
Yingcong
Y
Yu
Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, 325400, China.
Meixi
M
Zhang
Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, 325400, China.
Lichao
L
Chen
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China.
Weijie
W
Wang
WenLing Hospital of Traditional Chinese Medicine, Wenling, Zhejiang Province, 317500, China.
Weihong
W
Lv
Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, 310006, China.
Ling
L
Chen
Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, 310006, China.
Jiejin
J
Zhu
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325021, China.
Jianchun
J
Pan
Department of Behavioral Medicine & Psychiatry, West Virginia University, Morgantown, WV, 26505, USA.
Hanting
H
Zhang
Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325021, China; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA. Electronic address: yxu9@buffalo.edu.
Ying
Y
Xu
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. Electronic address: dlshu@163.com.
Lianshu
L
Ding
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D013267:Stilbenes; D007099:Imipramine; D000077185:Resveratrol
BDNF; Hypothalamus–pituitary–adrenal axis; Middle cerebral artery occlusion (MCAO); Post-stroke depression (PSD); Trans-resveratrol