Chronic effects of venlafaxine on synaptophysin and neuronal cell adhesion molecule in the hippocampus of cerebral ischemic mice.
Venlafaxine, a novel antidepressant, inhibits serontonin and norepinephrine reuptake in the presynaptic cleft. Unlike typical selective serontonin reuptake inhibitors (SSRIs), venlafaxine may have modulatory effects on nerve terminals and neuronal plasticity. Our preliminary data found that 5 mg.kg-1.d-1 of venlafaxine treatment prevented decreased synaptophysin (SYP) in the hippocampus, which results from chronic restrained stress in the rat model. The present study investigates whether venlafaxine regulates alterations of synaptophysin and neuronal cell adhesion molecule (NCAM) in a post-stroke depression mouse model. We compared the expression level of SYP and NCAM in the hippocampus of global cerebral ischemic (GCI) mice treated with different doses of venlafaxine using immunohistological and Western blot analysis. Pre-treatment with intraperitoneal injection of venlafaxine (2.5 and 5.0 mg.kg-1.d-1) for 14 days significantly prevented the decrease of SYP in the hilus area of the hippocampus in vehicle-treated GCI mice. NCAM was significantly higher in the hippocampus of vehicle-treated GCI mice, and pretreatment with venlafaxine prevented alterations of NCAM, with the high-dose venlafaxine group comparable with vehicle-sham mice. The results suggest the alteration of neuronal remodeling proteins in the hippocampus may be an underlying mechanism of venlafaxine in treating post-stroke depression.
Fang
Shaokuan
S
Department of Neurology, The First Teaching Hospital of Jilin University, Changchun, People's Republic of China.
Yan
Bin
B
Wang
Daoyi
D
Bi
Xiaoying
X
Zhang
Yanbo
Y
He
Jue
J
Xu
Haiyun
H
Yang
Yi
Y
Kong
Jiming
J
Wu
Jiang
J
Li
Xin-Min
XM
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003511:Cyclohexanols / Q000494:pharmacology*; D003866:Depressive Disorder / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism*; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D039842:Neural Cell Adhesion Molecule L1; D017367:Selective Serotonin Reuptake Inhibitors; D016708:Synaptophysin; D000069470:Venlafaxine Hydrochloride