Effects of environmental enrichment and sexual dimorphism on the expression of cerebellar receptors in C57BL/6 and BTBR + Itpr3tf/J mice

Abstract

Objective: Environmental enrichment is used to treat social, communication, and behavioral deficits and is known to modify the expression of synaptic receptors. We compared the effects of environmental enrichment in the expression of glutamate and endocannabinoid receptors, which are widely expressed in the cerebellar cortex. These two receptors interact to regulate neuronal function and their dysregulation is associated with behavioral changes. We used BTBR + Itpr3tf/J mice, a strain that models behavioral disorders, and C57BL/6 mice for comparison. We studied the effects of genetic background, sex, environmental conditions, and layer of the cerebellar cortex on the expression of each receptor. Results: The influence of genetic background and environmental enrichment had the same pattern on glutamate and endocannabinoid receptors in males. In contrast, in females, the effect of environmental enrichment and genetic background were different than the ones obtained for males and were also different between the glutamate and endocannabinoid receptors. Furthermore, an analysis of both receptors from tissue obtained from the same animals show that their expression is correlated in males, but not in females. Our results suggest that environmental enrichment has a receptor dependent and sexual dimorphic effect on the molecular expression of different receptors in the cerebellar cortex.