Brain inhibitory GABAergic function and cognitive deficits in depression and during aging: Mechanisms and therapeutic targeting
Seminar
- Date: Dec 17, 2019
- Time: 10:00 AM - 11:00 AM (Local Time Germany)
- Speaker: Dr. Etienne Sibille
- Professor, Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Canada
- Location: Max-Planck-Institut für Psychiatrie
- Room: Hörsaal
- Host: Dr Juan Pablo Lopez
- Contact: jplopez@psych.mpg.de
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.