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

Neurobiol Dis. 2008 Jun;30(3):312-322. doi: 10.1016/j.nbd.2008.01.015. Epub 2008 Mar 10.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Disease Models, Animal
  • Disease Progression
  • Glutamine / genetics
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Huntington Disease / pathology*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / cytology*
  • Neurons / drug effects*
  • Neurons / physiology
  • Sertraline / pharmacology
  • Sertraline / therapeutic use*

Substances

  • Glutamine
  • Asparagine
  • Sertraline