Document Detail

Chronic hypoxia impairs murine hippocampal development and depletes the postnatal progenitor pool by attenuating mammalian target of rapamycin signaling.
MedLine Citation:
PMID:  21532529     Owner:  NLM     Status:  MEDLINE    
Chronic hypoxia (CH) is a major risk factor for impaired cognitive function in various disease states, particularly in the context of cyanotic congenital heart disease. Although most brain development occurs prenatally, the dentate gyrus (DG) of the hippocampus harbors progenitor stem cells that contribute to its ongoing development postnatally. It is unclear how exposure to CH might affect postnatal hippocampal development, so we used a transgenic mouse that expresses enhanced green fluorescent protein (eGFP) within this progenitor population to determine the effect of CH on the DG. We find that exposure to 10% oxygen from postnatal d 3 to 28 results in a smaller DG with long-term impairment of hippocampal neurogenesis. Because the mammalian target of rapamycin (mTOR) pathway is a well-known regulator of cell proliferation and growth and is sensitive to hypoxia, we investigated its activation on exposure to CH and find it to be attenuated specifically in neural progenitor cells. Systemic inhibition of the mTOR pathway using rapamycin also caused impairment of hippocampal neurogenesis that mimics exposure to CH. Our findings demonstrate that CH results in long-term impairment of hippocampal neurogenesis and is mediated, in part, by attenuation of the mTOR pathway.
Lakshmi Raman; Xiangmei Kong; Jennifer A Gilley; Steven G Kernie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  70     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-07     Completed Date:  2011-11-15     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-65     Citation Subset:  IM    
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MeSH Terms
Blotting, Western
DNA Primers / genetics
Dentate Gyrus / cytology*,  growth & development*
Green Fluorescent Proteins / metabolism
Hypoxia, Brain / physiopathology*
Mice, Transgenic
Neurogenesis / physiology*
Polymerase Chain Reaction
Signal Transduction / physiology*
Stem Cells / physiology*
TOR Serine-Threonine Kinases / metabolism*
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; EC Serine-Threonine Kinases; EC protein, mouse

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