Journal article
Effects of prenatal exposure to ethanol on the cyclin-dependent kinase system in the developing rat cerebellum
Brain research. Developmental brain research, Vol.139(2), pp.237-245
2002
DOI: 10.1016/S0165-3806(02)00573-4
PMID: 12480138
Abstract
Prenatal exposure to ethanol inhibits neurogenesis in the developing cerebellum. Cyclin-dependent kinases (CDKs) are a family of protein kinases that play multiple roles in the regulation of cell proliferation, differentiation and survival. The activity of CDKs is positively regulated by CDK activators, cyclins, and negatively regulated by CDK inhibitors (CDKIs). We hypothesize that impaired cerebellar development induced by gestational ethanol exposure is mediated by disruption of the CDK system. Pregnant rats were fed ad libitum with an ethanol-containing liquid diet (Et) or pair-fed an isocaloric control diet (Ct). Cerebella were collected from pups (postnatal day (P) 0 through P21) and examined for CDK, cyclin, or CDKI expression using a quantitative immunoblotting procedure. In Ct-treated rats, the expression of CDK2 and its activator, cyclin A, paralleled the pattern of granule cell proliferation. Prenatal ethanol exposure produced a significant down-regulation of CDK2/cyclin A expression. Although the amounts of CDK4/CDK6 and their activator, cyclin D2, did not oscillate during postnatal development, their expression in Et-treated pups was significantly (
P<0.05) higher than in controls. The expression of a CDK inhibitor, p27
Kip, was inversely correlated to proliferation of cerebellar granule progenitors. Prenatal ethanol exposure caused the down-regulation of p27
Kip between P0 and P21. Thus, prenatal exposure to ethanol disturbed the expression of cell cycle machineries in the postnatal cerebellum. This may account for the teratogenic effects of ethanol on the developing cerebellum.
Details
- Title: Subtitle
- Effects of prenatal exposure to ethanol on the cyclin-dependent kinase system in the developing rat cerebellum
- Creators
- Zheng Li - West Virginia UniversityMichael W Miller - State University of New YorkJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Brain research. Developmental brain research, Vol.139(2), pp.237-245
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0165-3806(02)00573-4
- PMID
- 12480138
- ISSN
- 0165-3806
- Language
- English
- Date published
- 2002
- Academic Unit
- Pathology
- Record Identifier
- 9984186491402771
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