Environmental stimulation in Huntington disease patients and animal models

Neurobiol Dis. 2022 Sep:171:105725. doi: 10.1016/j.nbd.2022.105725. Epub 2022 Apr 12.

Abstract

While Huntington disease (HD) is caused solely by a polyglutamine expansion in the huntingtin gene, environmental factors can influence HD onset and progression. Here, we review studies linking environment and HD in both humans and animal models. In HD patients, we find that: (i) an active lifestyle associates with both a delayed age at onset of HD and a decreased severity of symptoms, (ii) applying physical exercise and behavioral therapies in small cohorts of HD subjects indicate promising effects on the HD symptomatology, (iii) Mediterranean diet correlates with lower motor impairment, and treatments based on omega-3 fatty acids improve motor function , whereas (iv) increased cortisol levels associate with specific HD symptoms. In animal models, in line with the evidence in humans, physical exercise, environmental enrichment and different types of dietary intervention ameliorate or delay several HD phenotypes. In contrast, stress appears to be involved in the HD pathogenesis, and HD mice present increased stress sensitivity. Importantly, studies in animal models have uncovered several molecular factors mediating environmental effects on HD associated neuropathology. However, the influence of the environment on several key HD mechanisms as well as the underlying regulatory factors remain to be explored. Given the role of epigenetic factors and modifications in the interplay between environment and genes, the exploration of their role as mechanisms underlying the environmental action in HD is a promising avenue for both our fundamental understanding of the disease and as a potential for therapy.

Keywords: Environmental enrichment; Huntington disease; dietary intervention; epigenetics; neuronal plasticity; physical exercise; stress; transcriptional dysregulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Environment*
  • Humans
  • Huntingtin Protein
  • Huntington Disease* / genetics
  • Huntington Disease* / pathology
  • Huntington Disease* / therapy
  • Mice
  • Mice, Transgenic

Substances

  • Huntingtin Protein