Journal article
Mechanisms of ethanol-induced death of cerebellar granule cells
Cerebellum (London, England), Vol.11(1), pp.145-154
03/2012
DOI: 10.1007/s12311-010-0219-0
PMCID: PMC3355343
PMID: 20927663
Abstract
Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that are most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of N-methyl-D-aspartate receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis.
Details
- Title: Subtitle
- Mechanisms of ethanol-induced death of cerebellar granule cells
- Creators
- Jia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Cerebellum (London, England), Vol.11(1), pp.145-154
- DOI
- 10.1007/s12311-010-0219-0
- PMID
- 20927663
- PMCID
- PMC3355343
- NLM abbreviation
- Cerebellum
- ISSN
- 1473-4222
- eISSN
- 1473-4230
- Grant note
- AA015407 / NIAAA NIH HHS AA017226 / NIAAA NIH HHS R01 AA015407 / NIAAA NIH HHS R21 AA019693 / NIAAA NIH HHS R01 AA017226 / NIAAA NIH HHS AA019693 / NIAAA NIH HHS
- Language
- English
- Date published
- 03/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984201256302771
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