Professor Etienne Sibille - Campbell Family Mental Health Research Institute, Canada : "GABA and Cognitive Deficits in Depression and Aging: Origins, Mechanisms and Therapeutics"
Professor Etienne Sibille
Campbell Family Mental Health Research Institute
Canada
Chair and Senior Scientist, Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, Canada,
Professor, Departments of Psychiatry and, of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
Title: GABA and Cognitive Deficits in Depression and Aging: Origins, Mechanisms and Therapeutics
Changes in the brain excitation inhibition balance characterize neuropsychiatric disorders and aging. Using human post-mortem samples and genetic rodent models, combined with genomic and bioinformatics approaches, we have reported changes in GABAergic inhibitory neurons that target pyramidal cell dendrites in human depression and aging, and associated these changes with cognitive and mood behaviors in rodent models. Using molecular modeling, medicinal chemistry, pharmacological approaches and rodent behavioral models, we now show that novel molecules that activate alpha5-containing GABA-A receptor, which mediate the function of dendritic-targeting GABAergic neurons, show robust pro-cognitive, anxiolytic and antidepressant effects in adult and age mice. Collectively the results suggest a novel therapeutic approach for the unmet need of reducing cognitive symptoms across brain disorders.
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