Conférence CRNL Anthony J Hannan "Gene-environment interactions modulating brain function within and between generations"

We are interested in how gene-environment interactions mediate and modulate brain function, in health and disease. Our findings have revealed key pathways implicated in the therapeutic impacts of environmental stimuli and identified novel therapeutic targets. We have also discovered altered brain-body interactions, including the first evidence of gut dysbiosis (dysregulated gastrointestinal microbiota) in Huntington’s disease (where we model depression, dementia and motor symptoms) and a genetic model of schizophrenia. We have found that environmental interventions which have therapeutic impacts also modulate the gut microbiome. Furthermore, we have shown that a high-fibre diet and prebiotic interventions improved gut function and ameliorated cognitive and affective dysfunction. Ongoing studies are exploring the gut microbiome as a therapeutic target and the possibility that specific environmental factors may modulate brain function via microbiota-gut-brain interactions. These approaches to gene-environment interactions may facilitate the development of enviromimetics (including exercise mimetics as a subclass) for various brain disorders.

In order to understand how gene-environment interactions may sculpt brain development and function between generations, we have also been exploring epigenetic inheritance via the paternal lineage. We have discovered transgenerational effects of various paternal environmental exposures, including exercise, stress and immune activation. These lifestyle factors and experiences modulate sperm noncoding RNAs and alter affective behaviors in offspring. We are exploring epigenetically mediated changes in the brains of offspring, including microglial activation states and other forms of neuroimmune modulation. The effects on offspring, including modulation of brain function and behavior, via epigenetic inheritance, have particular relevance to the pathogenesis of depression and anxiety disorders.