期刊
NEUROSCIENCE
卷 285, 期 -, 页码 281-291出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2014.11.025
关键词
acetyl-L-carnitine; brain-derived neurotrophic factor; phosphatidylinositol 3-kinase; depression; neuropeptide VGF
资金
- National Natural Science Foundation of China [81201050, 81171036]
- Natural Science Foundation of Zhejiang Province [LQ12H09001]
- Natural Science Foundation of Ningbo [2012A610249]
- Innovative Research Team of Ningbo [2009B21002]
- Natural Science Foundation of Ningbo University [XKL11D2111]
- Student Research and Innovation Program (SRIP) of Ningbo University
- Ningbo University
The possible involvement of the PI3K/AKT/BDNF/VGF signaling in rapid-acting antidepressant-like effects of antidepressants has been explored progressively by more studies. However, whether this signaling participates in the antidepressant-like effects of acetyl-L-carnitine (ALC) has not been examined. Herein, we assessed the antidepressant-like effects of ALC using the forced swimming test (FST). Our results demonstrated the dose-effect relationship of acute administration of ALC (5, 25, 50 and 100 mg/ kg, i.p.) and showed that it dose-dependently decreased the immobility time on FST of mice. In addition, ALC (100 mg/kg, i.p.) also reversed depressive-like behavior and the down-regulation of phosphorylated AKT (pAKT), brain-derived neurotrophic factor (BDNF) and neuropeptide VGF in the hippocampus and prefrontal cortex of mice induced by chronic unpredictable mild stress (CUMS) paradigm. Further, intra-cerebroventricular (i.c.v.) infusions of LY294002 (10 nmol/side), a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly prevented the antidepressant-like effect of ALC (100 mg/kg, i.p.). In conclusion, our results demonstrated that ALC exerts rapid-acting antidepressant-like effects that might be mediated by the PI3K/AKT/BDNF/VGF signaling pathway. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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