Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease

被引：109

作者：

Duan, Wenzhen ^{[1
]}

Peng, Qi ^{[1
]}

Masuda, Naoki ^{[1
]}

Ford, Eric ^{[2
]}

Tryggestad, Erik ^{[2
]}

Ladenheim, Bruce ^{[3
]}

Zhao, Ming

Cadet, Jean Lud ^{[3
]}

Wong, John ^{[2
]}

Ross, Christopher A. ^{[1
,4
,5
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Div Neurobiol, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21218 USA

[3] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Baltimore, MD 21224 USA

[4] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 30卷 / 03期

关键词：

SSRL; serotonin; BDNF; Huntington's disease; neurogenesis;

D O I：

10.1016/j.nbd.2008.01.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：312 / 322

页数：11

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