The Effects of Environmental Enrichment on the Autism-like Behaviors of the BTBR Mouse Strain

Abstract

BTBR T+ Itpr3tf/J (BTBR) mice are an Autism Spectrum Disorder (ASD)-like model and are characterized by similar behavioral and psychological symptoms as those presenting in patients with ASD. Such symptoms include difficulty in communication, impaired sociability, and increased engagement in repetitive stereotypic behaviors. Behavioral therapy is a common treatment for human ASD, but such non-pharmacological interventions remain to be explored in murine models. Here, we explored the effects of environmental enrichment (EE)—a housing condition consisting of larger space, running wheels, toys, etc. designed to stimulate complex social and cognitive engagement—in alleviating the symptoms of ASD. Juvenile BTBR mice were placed in standard or EE housing for 17 weeks while undergoing several behavioral and metabolic assessments. Following EE-exposure, male BTBR mice displayed reduced adiposity, increased lean mass, improved glycemic control, and decreased circulating leptin. Regarding behavior, EE-BTBR males displayed decreased anxiety and improved social affiliation but no changes in repetitive behaviors or social memory. Additionally, a gene expression profile of males showed an EE-induced upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in several brain regions. Contrarily, female BTBR responded less readily to EE, displaying only modest adipose remodeling and no changes in glycemic control, circulating leptin, anxiety, sociability, or repetitive behaviors. These results suggest that EE improves metabolic and some behavioral phenotypes in a sexually-dimorphic manner in BTBR mice.