Document Detail


Environmental enrichment rescues postnatal neurogenesis defect in the male and female Ts65Dn mouse model of Down syndrome.
MedLine Citation:
PMID:  21865665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Down syndrome (DS), the most frequent genetic cause of intellectual disability and developmental delay, results from impaired neural stem cell proliferation and differentiation. Impaired neurogenesis in the neocortex, hippocampus and cerebellum is believed to be the underlying cause of learning and behavioral deficits in the Ts65Dn mouse model of DS. Aggressive sensorimotor and cognitive therapies have shown promise in mitigating the cognitive disabilities in DS but these behavioral therapies have not yet been investigated at the cellular level. Here, using the Ts65Dn mouse model of DS, we demonstrate that a combination of environmental enrichment and physical exercise starting in juvenile mice (postnatal day 18) markedly increases cell proliferation, neurogenesis and gliogenesis in the hippocampal dentate gyrus (DG) and the forebrain subventricular zone (SVZ) of both male and female mice. Enrichment and exercise increased the rate of Ts65Dn DG neurogenesis to be comparable to that of the nonenriched euploid group, while the effect on SVZ neurogenesis was reduced and seen only after prolonged exposure. These results clearly indicate that in a comprehensive stimulatory environment, the postnatal DS brain has the intrinsic capability of improving neurogenesis and gliogenesis to the levels of normal matched controls and that this cellular response underlies the cognitive improvement seen following behavioral therapies.
Authors:
Lina Chakrabarti; Joseph Scafidi; Vittorio Gallo; Tarik F Haydar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-25
Journal Detail:
Title:  Developmental neuroscience     Volume:  33     ISSN:  1421-9859     ISO Abbreviation:  Dev. Neurosci.     Publication Date:  2011  
Date Detail:
Created Date:  2011-12-13     Completed Date:  2012-04-16     Revised Date:  2013-08-07    
Medline Journal Info:
Nlm Unique ID:  7809375     Medline TA:  Dev Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  428-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight
Cell Proliferation
Disease Models, Animal
Down Syndrome / pathology,  physiopathology*
Environment*
Female
Hippocampus / cytology
Humans
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Motor Activity
Neurogenesis / physiology*
Grant Support
ID/Acronym/Agency:
HD001399/HD/NICHD NIH HHS; K12 NS052/NS/NINDS NIH HHS; P01NS062686/NS/NINDS NIH HHS; P30 HD40677/HD/NICHD NIH HHS; R01 HD057580/HD/NICHD NIH HHS; R01 HD057580/HD/NICHD NIH HHS; R01 NS045702/NS/NINDS NIH HHS; R01 NS056427/NS/NINDS NIH HHS; R01 NS076503/NS/NINDS NIH HHS
Comments/Corrections

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