The role of progestogen neurosteroids in behaviors relevant for autism spectrum disorders.

摘要

Autism spectrum disorder (ASD) affects children across the U.S. and is characterized by deficits in social communication and restrictive/repetitive behaviors, for which few therapeutic interventions have been successful. Steroid hormones, such as progesterone (P4) and its metabolite, 5&agr;-pregnan-3&agr;-ol-20-one (3&agr;,5&agr;-THP), can exert neuroprotective effects, influence synaptic morphology, mediate behavioral outcomes, and influence stress-responding. In this thesis, the behaviors and baseline levels of the stress hormone, corticosterone, P4, and 3&agr;,5&agr;-THP are investigated in BTBR T+ Itpr3tf/J (BTBR) mice, a proposed ASD model. It was hypothesized that BTBR mice would show abnormalities in behaviors and in levels of steroids and neuroendocrine factors. Results from Experiment 1 indicate that BTBR mice demonstrate deficits in social behaviors and elevated affective and repetitive behaviors. Results from Experiment 2 demonstrate that BTBR mice have elevated levels of corticosterone, P4, and 3&agr;,5&agr;-THP. These findings suggest that neuroendocrine dysregulation may partly underlie the ASD-like behavioral phenotype of BTBR mice.