Sex-Dependent Effects of Environmental Enrichment on Spatial Memory and Brain-Derived Neurotrophic Factor (BDNF) Signaling in a Developmental "Two-Hit" Mouse Model Combining BDNF Haploinsufficiency and Chronic Glucocorticoid Stimulation

Abstract

Neurodevelopmental disorders are thought to be caused by a combination of adverse genetic and environmental insults. The "two-hit" hypothesis suggests that an early first "hit" primes the developing brain to be vulnerable to a second "hit" during adolescence which triggers behavioral dysfunction. We have previously modeled this scenario in mice and found that the combined effect of a genetic hapolinsuffuciency in the brain-derived neurotrophic factor (BDNF) gene (1st hit) and chronic corticosterone (CORT) treatment during adolescence (2nd hit), caused spatial memory impairments in adulthood. Environmental enrichment (EE) protocols are designed to stimulate experience-dependent plasticity and..