PMID- 25587342 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150114 LR - 20200930 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2014 DP - 2014 TI - Antidepressant-like effects of cordycepin in a mice model of chronic unpredictable mild stress. PG - 438506 LID - 10.1155/2014/438506 [doi] LID - 438506 AB - Cordycepin (3'-deoxyadenosine), a major bioactive component isolated from Cordyceps militaris, has multiple pharmacological activities. This study is attempted to investigate whether cordycepin (COR) possesses beneficial effects on chronic unpredictable mild stress- (CUMS-) induced behavioral deficits (depression-like behaviors) and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR and fluoxetine (FLU, positive control drug) were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests, open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), were applied to evaluate the antidepressant effects of COR. Then the serotonin (5-HT) and noradrenaline (NE) concentrations in hippocampal were evaluated by HPLC; tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hippocampal were evaluated, and the proteins of TNF-alpha, IL-6, NF-kappaBP65 5-HT2A receptor (5-HT2AR), and brain-derived neurotrophic factor (BDNF) in hippocampal were evaluated by Western blot. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with low 5-HT and NE levels, high TNF-alpha and IL-6 in brain and high hippocampal TNF-alpha, IL-6, P-NF-kappaBP65, and 5-HT2AR levels, and low BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure, treatment with COR normalized the change of TNF-alpha, IL-6, 5-HT, and NE levels, which demonstrated that COR could partially restore CUMS-induced 5-HT receptor impairments and inflammation. Besides, hippocampal BDNF expressions were also upregulated after COR treatments. In conclusion, COR remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the upregulating BDNF and downregulating 5-HT2AR levels and inflammation in hippocampus. FAU - Tianzhu, Zhang AU - Tianzhu Z AD - Changchun University of Chinese Medicine, Changhcun 130117, China. FAU - Shihai, Yang AU - Shihai Y AD - Jilin Agricultural University, Changchun 130118, China. FAU - Juan, Du AU - Juan D AD - School of Life Science, Peking University, Beijing 100871, China. LA - eng PT - Journal Article DEP - 20141223 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC4284936 EDAT- 2015/01/15 06:00 MHDA- 2015/01/15 06:01 PMCR- 2014/12/23 CRDT- 2015/01/15 06:00 PHST- 2014/08/22 00:00 [received] PHST- 2014/10/31 00:00 [revised] PHST- 2014/12/03 00:00 [accepted] PHST- 2015/01/15 06:00 [entrez] PHST- 2015/01/15 06:00 [pubmed] PHST- 2015/01/15 06:01 [medline] PHST- 2014/12/23 00:00 [pmc-release] AID - 10.1155/2014/438506 [doi] PST - ppublish SO - Evid Based Complement Alternat Med. 2014;2014:438506. doi: 10.1155/2014/438506. Epub 2014 Dec 23.