Document Detail


Enforced Pax6 expression rescues alcohol-induced defects of neuronal differentiation in cultures of human cortical progenitor cells.
MedLine Citation:
PMID:  22524987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Alcohol is the most widely consumed substance of abuse, and its use during pregnancy can lead to serious disorders of brain development. The precise molecular action of alcohol on human brain development, however, is still unknown. We previously enriched multipotent progenitor cells, radial glia (RG) cells, from human fetal forebrain and demonstrated that they express transcription factor Pax6 that is necessary for their neurogenic fate.
METHODS: Enriched human fetal RG cells were maintained in vitro as either control or Pax6-expressing retrovirus infected cells. Cultures were treated with increasing doses of alcohol to evaluate Pax6 expression, proliferation, and differentiation of RG cells by immunocytochemistry, Western blot, and RT-PCR methods.
RESULTS: In vitro treatment with alcohol reduced the expression of transcription factor Pax6 and proliferation of RG cells, which decreased neurogenesis. Consistent with this finding, the overexpression of Pax6 in RG cells under alcohol treatment rescued cell proliferation and restored the generation of neurons. In contrast to this effect on neurogenesis, the overexpression of Pax6 inhibits the generation of astroglia regardless of alcohol treatment, implying lineage-specific effects.
CONCLUSIONS: These findings suggest that the effect of alcohol on human neurogenesis is partially due to the reduced expression of transcription factor Pax6 in RG cells.
Authors:
Zhicheng Mo; Verica Milivojevic; Nada Zecevic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-23
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  36     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-06     Completed Date:  2012-12-11     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1374-84     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 by the Research Society on Alcoholism.
Affiliation:
Department of Neuroscience, University of Connecticut Health Center, Farmington, 06030-3401, USA.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites / diagnostic use
Bromodeoxyuridine / diagnostic use
Cell Count
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Central Nervous System Depressants / pharmacology*
Cerebral Cortex / cytology*
Dose-Response Relationship, Drug
Ethanol / pharmacology*
Eye Proteins / biosynthesis,  genetics,  physiology*
Female
Homeodomain Proteins / biosynthesis,  genetics,  physiology*
Humans
Immunohistochemistry
Neural Stem Cells / drug effects*
Neurogenesis / drug effects
Neurons / drug effects*
Paired Box Transcription Factors / biosynthesis,  genetics,  physiology*
Pregnancy
Real-Time Polymerase Chain Reaction
Repressor Proteins / biosynthesis,  genetics,  physiology*
Retroviridae / genetics
Grant Support
ID/Acronym/Agency:
5T32 NS041224/NS/NINDS NIH HHS; NS41489/NS/NINDS NIH HHS; R01 NS041489/NS/NINDS NIH HHS; R01 NS041489-11/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Central Nervous System Depressants; 0/Eye Proteins; 0/Homeodomain Proteins; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Repressor Proteins; 59-14-3/Bromodeoxyuridine; 64-17-5/Ethanol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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