Cerebellar Interpositus Nucleus Transcriptome Following Early-Life Limited Bedding Stress in P70 Male and Female Rats

Purpose: This particular experiment is part of a broader study on the effects of early-life stress on the cerebellar endocannabinoid system. Early-life stress is a major developmental risk factor. Though studies are now considering the endogenous cannabinoid system, which is highly intertwied with the stress-response, as a moderator of these effects, studies have been largely focused on cerebral effects. Cerebellum is vulnerable to stress during early development and is dense with cannabinoid receptors, making it an important target for stress effects. Moreover, relatively little is known about sex-specific effects in cerebellum. Methods: Limited bedding, a naturalistic rodent model of early-life stress, was performed at postnatal days 2-9. Following, rats were reared normally and adult (postnatal day 70) cerebellar interpositus nucleus mRNA was assessed. Results: Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Specifically, expression of 25% of the genes evaluated significantly differed by sex alone. Interestingly, in the non-stressed groups, there were significant sex differences in Cnr1, cannabinoid receptor 1. Conclusion: We show robust sex-specific transcriptomics effects in cerebellar interpositus, perhaps suggesting a role for this system in sexual differentiation of the brain. Other regions of cerebellum should be evaluated. Cerebellar interpositus nucleus mRNA profiles were obtain for 70 day old Long-Evans rats with or without early-life limited bedding stress. 27 total samples were analyzed including 8 replicates of males having undergone limited bedding stress, 7 replicates of females having undergone limited bedding stress, 7 replicates of control males reared normally, and 6 replicates of control females reared normally.