Sustained Mobilization of Endogenous Neural Progenitors Delays Disease Progression in a Transgenic Model of Huntington's Disease

被引：48

作者：

Benraiss, Abdellatif ^{[1
,2
]}

Toner, Michael J. ^{[1
,2
]}

Xu, Qiwu ^{[2
,3
]}

Bruel-Jungerman, Elodie ^{[1
,3
]}

Rogers, Eloise H. ^{[1
]}

Wang, Fushun ^{[2
,3
]}

Economides, Aris N. ^{[4
]}

Davidson, Beverly L. ^{[5
]}

Kageyama, Ryoichiro ^{[6
]}

Nedergaard, Maiken ^{[2
,3
]}

Goldman, Steven A. ^{[1
,2
,3
]}

机构：

[1] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA

[2] Univ Rochester, Med Ctr, Dept Neurosurg, Rochester, NY 14642 USA

[3] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA

[4] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

[5] Univ Iowa, Dept Med, Iowa City, IA 52242 USA

[6] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan

来源：

CELL STEM CELL | 2013年 / 12卷 / 06期

关键词：

NEURONAL INTRANUCLEAR INCLUSIONS; STEM-CELLS; ADULT FOREBRAIN; SPINY NEURONS; GENE-THERAPY; MOUSE MODEL; BRAIN; MICE; NEUROGENESIS; EXPRESSION;

D O I：

10.1016/j.stem.2013.04.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Huntington's disease (HD) is a neurodegenerative disease characterized in part by the loss of striatopallidal medium spiny projection neurons (MSNs). Expression of BDNF and noggin via intracerebroventricular (ICV) delivery in an adenoviral vector triggers the addition of new neurons to the neostriatum. In this study, we found that a single ICV injection of the adeno-associated viruses AAV4-BDNF and AAV4-noggin triggered the sustained recruitment of new MSNs in both wild-type and R6/2 mice, a model of HD. Mice treated with AAV4-BDNF/noggin or with BDNF and noggin proteins actively recruited subependymal progenitor cells to form new MSNs that matured and achieved circuit integration. Importantly, the AAV4-BDNF/noggin-treated R6/2 mice showed delayed deterioration of motor function and substantially increased survival. In addition, squirrel monkeys given ICV injections of adenoviral BDNF/ noggin showed similar addition of striatal neurons. Induced neuronal addition may therefore represent a promising avenue for disease amelioration in HD.

引用

页码：787 / 799

页数：13

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