17 24

Cited 0 times in

In Vivo Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington's Disease

Authors
 Ji-Hea Yu  ;  Bae-Geun Nam  ;  Min-Gi Kim  ;  Soonil Pyo  ;  Jung-Hwa Seo  ;  Sung-Rae Cho 
Citation
 GENES, Vol.12(5) : 712, 2021-05 
Journal Title
GENES
Issue Date
2021-05
Keywords
Huntington’s disease ; octamer-binding transcription factor 4 ; oligodendrocyte progenitor cells ; reprogramming
Abstract
White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington's disease (HD). This study investigated the effects of in vivo expression of reprogramming factor octamer-binding transcription factor 4 (OCT4) on neural stem cell (NSC) niche activation in the subventricular zone (SVZ) and induction of cell fate specific to the microenvironment of HD. R6/2 mice randomly received adeno-associated virus 9 (AAV9)-OCT4, AAV9-Null, or phosphate-buffered saline into both lateral ventricles at 4 weeks of age. The AAV9-OCT4 group displayed significantly improved behavioral performance compared to the control groups. Following AAV9-OCT4 treatment, the number of newly generated NSCs and oligodendrocyte progenitor cells (OPCs) significantly increased in the SVZ, and the expression of OPC-related genes and glial cell-derived neurotrophic factor (GDNF) significantly increased. Further, amelioration of myelination deficits in the corpus callosum was observed through electron microscopy and magnetic resonance imaging, and striatal DARPP32+ GABAergic neurons significantly increased in the AAV9-OCT4 group. These results suggest that in situ expression of the reprogramming factor OCT4 in the SVZ induces OPC proliferation, thereby attenuating myelination deficits. Particularly, GDNF released by OPCs seems to induce striatal neuroprotection in HD, which explains the behavioral improvement in R6/2 mice overexpressing OCT4.
Files in This Item:
T202102062.pdf Download
DOI
10.3390/genes12050712
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/22282913/184081
사서에게 알리기
  feedback

qrcode

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

Browse

Links