Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period
| العنوان: | Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period |
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| المؤلفون: | Cynthia J.M. Kane, Rajesh C. Miranda, Marisa R Pinson, James C. Douglas, Paul D. Drew, Kalee N Holloway |
| المصدر: | Alcohol Clin Exp Res |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, endocrine system, Cerebellum, Neurogenesis, Medicine (miscellaneous), Apoptosis, Biology, Hippocampal formation, Toxicology, Hippocampus, Article, Transcriptome, Biological pathway, Mice, Interneurons, Pregnancy, mental disorders, medicine, Animals, Hippocampus (mythology), RNA, Messenger, reproductive and urinary physiology, Ethanol, Cell Cycle, Gene Expression Regulation, Developmental, Teratology, Oligodendrocyte, Cell biology, Mice, Inbred C57BL, Psychiatry and Mental health, medicine.anatomical_structure, Animals, Newborn, nervous system, Female |
| الوصف: | Background The developing hippocampus and cerebellum, unique among brain regions, exhibit a secondary surge in neurogenesis during the third trimester of pregnancy. Ethanol (EtOH) exposure during this period is results in a loss of tissue volume and associated neurobehavioral deficits. However, mechanisms that link EtOH exposure to teratology in these regions are not well understood. We therefore analyzed transcriptomic adaptations to EtOH exposure to identify mechanistic linkages. Methods Hippocampi and cerebella were microdissected at postnatal day (P)10, from control C57BL/6J mouse pups, and pups treated with 4 g/kg of EtOH from P4 to P9. RNA was isolated and RNA-seq analysis was performed. We compared gene expression in EtOH- and vehicle-treated control neonates and performed biological pathway-overrepresentation analysis. Results While EtOH exposure resulted in the general induction of genes associated with the S-phase of mitosis in both cerebellum and hippocampus, overall there was little overlap in differentially regulated genes and associated biological pathways between these regions. In cerebellum, EtOH additionally induced gene expression associated with the G2/M-phases of the cell cycle and sonic hedgehog signaling, while in hippocampus, EtOH-induced the pathways for ribosome biogenesis and protein translation. Moreover, EtOH inhibited the transcriptomic identities associated with inhibitory interneuron subpopulations in the hippocampus, while in the cerebellum there was a more pronounced inhibition of transcripts across multiple oligodendrocyte maturation stages. Conclusions These data indicate that during the delayed neurogenic period, EtOH may stimulate the cell cycle, but it otherwise results in widely divergent molecular effects in the hippocampus and cerebellum. Moreover, these data provide evidence for region- and cell-type-specific vulnerability, which may contribute to the pathogenic effects of developmental EtOH exposure. |
| تدمد: | 1530-0277 0145-6008 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77908a69db34627294d774274ca97c19 https://doi.org/10.1111/acer.14633 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....77908a69db34627294d774274ca97c19 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15300277 01456008 |
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