Therapeutic Effects of Anthocyanins and Environmental Enrichment in R6/1 Huntington's Disease Mice

J Huntingtons Dis. 2016 Oct 1;5(3):285-296. doi: 10.3233/JHD-160204.

Abstract

Background: Huntington's disease (HD) is a progressive neurodegenerative disease with no effective treatment or cure. Environmental enrichment has been used to slow processes leading to ageing and neurodegenerative diseases including HD. Phenolic phytochemicals including anthocyanins have also been shown to improve brain function in ageing and neurodegenerative diseases.

Objective: This study examined the effects of anthocyanin dietary supplementation and environmental enrichment on behavioural phenotypes and brain cholesterol metabolic alterations in the R6/1 mouse model of HD.

Methods: R6/1 HD mice and their wild-type littermate controls were randomised into the different experimental conditions, involving either environmentally enriched versus standard housing conditions, or anthocyanin versus control diet. Motor dysfunction was assessed from 6 to 26 weeks using the RotaRod and the hind-paw clasping tests. Gas chromatography - tandem mass spectrometry was used to quantify a broad range of sterols in the striatum and cortex of R6/1 HD mice.

Results: Anthocyanin dietary supplementation delayed the onset of motor dysfunction in female HD mice. Environmental enrichment improved motor function and the hind paw clasping phenotype in male HD mice only. These mice also had lower levels of cholesterol oxidation products in the cortex compared to standard-housed mice.

Conclusion: Both anthocyanin supplementation and environmental enrichment are able to improve the motor dysfunction phenotype of R6/1 mice, however the effectiveness of these interventions was different between the two sexes. The interventions examined did not alter brain cholesterol metabolic deficits that have been reported previously in this mouse model of HD.

Keywords: Huntington disease; anthocyanins; cholesterol; dietary supplements; environment; housing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anthocyanins / administration & dosage*
  • Anthocyanins / therapeutic use
  • Body Weight / genetics
  • Brain / metabolism
  • Brain / pathology
  • Diet Therapy / methods*
  • Disease Models, Animal
  • Environment*
  • Female
  • Humans
  • Huntingtin Protein / genetics
  • Huntington Disease / diet therapy*
  • Huntington Disease / genetics
  • Huntington Disease / nursing*
  • Huntington Disease / pathology
  • Male
  • Mice, Transgenic
  • Motor Activity / physiology
  • Muscle Strength / genetics
  • Muscle Strength / physiology
  • Random Allocation
  • Sterols / metabolism
  • Tandem Mass Spectrometry
  • Trinucleotide Repeats / genetics

Substances

  • Anthocyanins
  • HTT protein, human
  • Huntingtin Protein
  • Sterols