BTBR T+ Itpr3tf/J (BTBR) mice are an Autism Spectrum Disorder (ASD)-like model that
exhibit behavioral and physiological deficits similar to those observed in patients
with ASD. While behavioral therapy is a first line of treatment in ASD patients, comparable
non-pharmacological treatments are less explored in murine models. Here, we administer
a bio-behavioral intervention for BTBR mice by way of environmental enrichment (EE)
— an experimental housing paradigm previously shown to improve systemic metabolism,
learning/memory, anxious behavior, neurogenesis, locomotion, and immunocompetence
in C57BL/6 mice. Juvenile BTBR mice were randomized to standard or EE housing and
were subjected to metabolic and behavioral assessments up to 17 weeks. Following EE
exposure, we report an EE-induced metabolic and behavioral phenotype. Male BTBR mice
responded metabolically to EE, displaying reduced adiposity, increased lean mass,
improved glycemic control, and decreased circulating leptin. The gene expressions
of brain-derived neurotrophic factor ( Bdnf ) and its receptor ( Ntrk2 / TrkB ) were
upregulated in several brain areas in EE-BTBR males. EE-BTBR females showed modest
reduction of adiposity and no changes in glycemic control, circulating leptin, or
Bdnf / Ntrk2 gene expression. With regard to behavior, EE resulted in decreased anxiety,
and increased social affiliation. Together, these results suggest that EE improves
metabolic and behavioral health in BTBR mice.