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

Wenzhen Duan, Qi Peng, Naoki Masuda, Eric Ford, Erik Tryggestad, Bruce Ladenheim, Ming Zhao, Jean Lud Cadet, John Wong, Christopher A. Ross

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)312-322
Number of pages11
JournalNeurobiology of Disease
Volume30
Issue number3
DOIs
StatePublished - Jun 1 2008

Keywords

  • BDNF
  • Huntington's disease
  • Neurogenesis
  • SSRI
  • Serotonin

ASJC Scopus subject areas

  • Neurology

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