title: MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade.
abstract: Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum.
authors.affiliation: From the Department of Molecular and Biomedical Pharmacology and.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Qi
authors.forename: Mingfang
authors.initials: M
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Frank
authors.forename: Lu
authors.initials: L
authors.lastname: Dai
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D005136:Eye Proteins; D018398:Homeodomain Proteins; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C105441:Rax protein, mouse; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D000431:Ethanol; D019892:eIF-2 Kinase
keywords: Apoptosis; Cerebellum; Ethanol; Fetal; MiR-29b; MicroRNA; Neurons; PKR; Signal Transduction