Speaker:

Prof. Anthony J. Hannan
NHMRC Principal Research Fellow
Florey Institute of Neuroscience and Mental Health
University of Melbourne

Title: "Gene-environment interactions informing therapeutic approaches for cognitive and affective disorders"

Abstract:

Huntington’s disease (HD) is one of over 50 tandem repeat disorders and involves neurodegeneration leading to psychiatric, cognitive and motor symptoms. In a transgenic mouse model of HD, expressing the tandem-repeat mutation, we have demonstrated that environmental enrichment (enhanced cognitive stimulation and physical activity) can delay onset of endophenotypes modelling depression, dementia and movement disorders. These findings have been extended to include exercise and stress models in HD mice, and environmental manipulations in mouse models of other neurological and psychiatric disorders, including autism, schizophrenia, depression and anxiety disorders. Our molecular and cellular investigations 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 microbiota) in HD, and a genetic mouse model of schizophrenia. 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 a variety of brain disorders known to be modulated by environmental stimuli.


In a parallel program of research, we have been exploring epigenetic inheritance via the paternal lineage. We have discovered the transgenerational effects of various paternal environmental exposures. Our findings reveal significant experience-dependent effects on cognitive and affective function of offspring via epigenetic inheritance. We are investigating the impacts of specific environmental and pharmacological factors, including exercise and stress-hormone elevation, and the relevance of these discoveries in mice to human transgenerational epigenetics and associated ‘epigenopathy’.  Our ongoing studies are exploring mechanisms whereby experience can modify germ cells and associated sperm epigenetics (including non-coding RNAs), and how these epigenetic modifications (of mice and men) may modulate offspring phenotypes and their potential susceptibility to various brain disorders.

 


 

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