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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE139953 | GEO | 2020/04/29

REPOSITORIES: GEO

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Project description:Purpose: Fetal alcohol spectrum disorders (FASD) result from ethanol exposure to the developing fetus. FASD occur in up to 1-5% of live births in the United States and there currently is no cure. Ethanol exposure to the developing central nervous system (CNS) has profound effects on learning and memory, impulse control, and motor function, resulting from neuropathology. The purpose of the current study was to perform transcriptome analysis to evaluate the effects of early postnatal ethanol exposure in the hippocampus and cerebellum. Methods: Postnatal C57BL/6 mice were treated with 4g/kg of ethanol from P4-P9, brains were harvested 24h after the final treatment at P10, hippocampi and cerebella were microdissected, RNA was isolated, and RNASeq analysis was performed. We compared differences in gene expression, sex-dependent expression, and global biological pathways associated with disruptions in hippocampal and cerebellar genes between the ethanol and vehicle treated neonates. Results: Ethanol caused both an up and down regulation of genes associated with the hippocampus and cerebellum, which may result in the disruption of normal circuitry and maturation and growth in these brain regions. Ethanol increased the expression of genes associated with the S phase of the cell cycle in both the hippocampus and cerebellum. In the cerebellum, ethanol increased effector gene expression, and in the hippocampus, genes associated with different interneuron lineages were altered. Postnatal ethanol exposure also resulted in altered expression of genes associated with oligodendrocyte lineages and myelination, along with alterations in microglia associated genes. Conclusion: Collectively, these data indicate that ethanol has profound effects on the hippocampus and cerebellum, resulting in alterations of gene expression and biological pathways regulating neurodevelopment. These studies may have important implications concerning alcohol-induced neuropathology and the neurological effects seen across the life span in FASD.

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

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