Amelioration of transcriptional disturbances in female BACHD rats by environmental enrichment

Abstract

Huntington’s disease is a devastating neuropsychiatric hereditary illness. While progressive in nature, there is evidence suggesting the disease can be positively modified through lifestyle changes. The influence of putative protective factors can be modelled in animal models by enriched environments. As of today, there is a wide array of different implementations of environmental enrichment with little comparative information regarding their respective effects. Aiming to better understand the connection between environmental stimulation and disease progression, we examined behavioural and striatal gene expression changes in female BACHD transgenic rats exposed to either a standard environment or one of two environmental enrichment protocols differing in tem poral onset. Our results show striking transgenic effects on phenotype and gene expression. Both glial and neuronal functions and cellular pathways were affected. When exposed to environmental enrichment, both protocols markedly reduced striatal dysregulation, yet some differences were observed between the two designs, thus inviting future studies to further examine the differential effects of specific paradigms. Our findings high light the promising potential of lifestyle interventions to lighten disease burden of patients and improving their quality of life.