| Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics. | |
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MedLine Citation:
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PMID: 21484803 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromodeoxyuridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis and also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure. |
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Authors:
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Justin A McClain; Dayna M Hayes; Stephanie A Morris; Kimberly Nixon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of comparative neurology Volume: 519 ISSN: 1096-9861 ISO Abbreviation: J. Comp. Neurol. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-07-20 Completed Date: 2011-11-15 Revised Date: 2013-04-05 |
Medline Journal Info:
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Nlm Unique ID: 0406041 Medline TA: J Comp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 2697-710 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Alcohol Drinking / adverse effects* Animals Cell Cycle / drug effects* Cell Proliferation / drug effects* Ethanol / blood, pharmacology*, poisoning Female Hippocampus / cytology* Humans Male Rats Rats, Sprague-Dawley Stem Cells / cytology, drug effects*, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AA016959/AA/NIAAA NIH HHS; R01 AA016959/AA/NIAAA NIH HHS; R21 AA0160307/AA/NIAAA NIH HHS; R21 AA016307/AA/NIAAA NIH HHS; T32 DA007304/DA/NIDA NIH HHS; T32 DA016176/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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64-17-5/Ethanol |
| Comments/Corrections | |
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