136 128

Cited 109 times in

Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease

Authors
 Sung-Rae Cho  ;  Abdellatif Benraiss  ;  Steven A. Goldman  ;  Aris Economides  ;  Amer Samdani  ;  Eva Chmielnicki 
Citation
 JOURNAL OF CLINICAL INVESTIGATION, Vol.117(10) : 2889-2902, 2007 
Journal Title
 JOURNAL OF CLINICAL INVESTIGATION 
ISSN
 0021-9738 
Issue Date
2007
MeSH
Adenoviridae/genetics ; Animals ; Brain-Derived Neurotrophic Factor/genetics* ; Carrier Proteins/genetics* ; Disease Models, Animal ; Disease Progression ; Enkephalins/analysis ; Enkephalins/metabolism ; Globus Pallidus/cytology ; Globus Pallidus/physiology ; Huntington Disease/physiopathology ; Huntington Disease/therapy* ; Mice ; Mice, Transgenic ; Mitosis ; Neostriatum/cytology ; Neostriatum/physiology* ; Neurons/chemistry ; Neurons/metabolism ; Neurons/physiology* ; Regeneration* ; Substance P/analysis ; Substance P/metabolism ; Tubulin/metabolism
Abstract
Ependymal overexpression of brain-derived neurotrophic factor (BDNF) stimulates neuronal addition to the adult striatum, from subependymal progenitor cells. Noggin, by suppressing subependymal gliogenesis and increasing progenitor availability, potentiates this process. We asked whether BDNF/Noggin overexpression might be used to recruit new striatal neurons in R6/2 huntingtin transgenic mice. R6/2 mice injected with adenoviral BDNF and adenoviral Noggin (AdBDNF/AdNoggin) recruited BrdU+βIII-tubulin+ neurons, which developed as DARPP-32+ and GABAergic medium spiny neurons that expressed either enkephalin or substance P and extended fibers to the globus pallidus. Only AdBDNF/AdNoggin-treated R6/2 mice harbored migrating doublecortin-defined neuroblasts in their striata, and the new neurons expressed p27 as a marker of mitotic quiescence after parenchymal integration. AdBDNF/AdNoggin-treated R6/2 mice sustained their rotarod performance and open-field activity and survived longer than did AdNull-treated and untreated controls. Neither motor performance nor survival improved in R6/2 mice treated only with AdBDNF, and intraventricular infusion of the mitotic inhibitor Ara-C completely blocked the performance and survival effects of AdBDNF/AdNoggin, suggesting that the benefits of AdBDNF/AdNoggin derived from neuronal addition. Thus, BDNF and Noggin induced striatal neuronal regeneration, delayed motor impairment, and extended survival in R6/2 mice, suggesting a new therapeutic strategy in Huntington disease.
Files in This Item:
T200700395.pdf Download
DOI
10.1172/JCI31778
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96261
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse