title: Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice.
abstract: 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 100mg/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 (100mg/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.
authors.affiliation: Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, PR China; Department of Pharmacy, Henan Cancer Hospital, Zhengzhou 450008, PR China; Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. Electronic address: wanglovechuang@163.com.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Cui
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. Electronic address: wangqinwen@nbu.edu.cn.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Ningbo Key Lab of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009414:Nerve Growth Factors; D009479:Neuropeptides / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009414:Nerve Growth Factors; D009479:Neuropeptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; C512697:Vgf protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000108:Acetylcarnitine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: acetyl-l-carnitine; brain-derived neurotrophic factor; depression; neuropeptide VGF; phosphatidylinositol 3-kinase