Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease

Exp Neurol. 2010 Sep;225(1):74-84. doi: 10.1016/j.expneurol.2010.05.006. Epub 2010 Jun 1.


Sirtuins are NAD-dependent deacetylases that regulate important biologic processes including transcription, cell survival and metabolism. Activation of SIRT1, a mammalian sirtuin, extends longevity and increases neuronal survival. An important substrate of SIRT1 is peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha), a principal regulator of energy metabolism, whose function is significantly impaired in Huntington's disease (HD). We studied the effects of a pharmacological preparation of the SIRT1 activator resveratrol (SRT501-M), in the N171-82Q transgenic mouse model of HD. We analyzed motor performance, survival, central and peripheral pathology and levels of PGC-1alpha expression. Administration of SRT501-M increased expression of PGC-1alpha, as well as its downstream targets, nuclear respiratory factor-1 (NRF-1) and uncoupling protein-1 (UCP-1) in brown adipose tissue (BAT), but there was no effect on PGC-1alpha, NRF-1 or the mitochondrial transcription factor (Tfam) in the striatum. SRT501-M administration also reduced BAT vacuolation and decreased elevated blood glucose levels. However, there was no significant improvement in weight loss, motor performance, survival and striatal atrophy. Activation of the PGC-1alpha signaling pathway via resveratrol-induced activation of SIRT1, therefore, is an effective therapy in BAT, but not in the central nervous system of HD transgenic mice.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Disease Models, Animal*
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Resveratrol
  • Sirtuin 1 / biosynthesis
  • Sirtuin 1 / deficiency
  • Sirtuin 1 / physiology
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use*
  • Trans-Activators / biosynthesis
  • Trans-Activators / deficiency
  • Trans-Activators / physiology
  • Transcription Factors
  • Treatment Outcome


  • Antioxidants
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Stilbenes
  • Trans-Activators
  • Transcription Factors
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Resveratrol