Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease

Abdellatif Benraiss; Michael J. Toner; Qiwu Xu; Elodie Bruel-Jungerman; Eloise H. Rogers; Fushun Wang; Aris N. Economides; Beverly L. Davidson; Ryoichiro Kageyama; Maiken Nedergaard; Steven A. Goldman

doi:10.1016/j.stem.2013.04.014

Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease

Abdellatif Benraiss, Michael J. Toner, Qiwu Xu, Elodie Bruel-Jungerman, Eloise H. Rogers, Fushun Wang, Aris N. Economides, Beverly L. Davidson, Ryoichiro Kageyama, Maiken Nedergaard, Steven A. Goldman

Department of Surgery

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Abstract

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.

Original language	English (US)
Pages (from-to)	787-799
Number of pages	13
Journal	Cell Stem Cell
Volume	12
Issue number	6
DOIs	https://doi.org/10.1016/j.stem.2013.04.014
State	Published - Jun 6 2013

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2013.04.014

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Benraiss, A., Toner, M. J., Xu, Q., Bruel-Jungerman, E., Rogers, E. H., Wang, F., Economides, A. N., Davidson, B. L., Kageyama, R., Nedergaard, M., & Goldman, S. A. (2013). Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease. Cell Stem Cell, 12(6), 787-799. https://doi.org/10.1016/j.stem.2013.04.014

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title = "Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease",

abstract = "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.",

author = "Abdellatif Benraiss and Toner, \{Michael J.\} and Qiwu Xu and Elodie Bruel-Jungerman and Rogers, \{Eloise H.\} and Fushun Wang and Economides, \{Aris N.\} and Davidson, \{Beverly L.\} and Ryoichiro Kageyama and Maiken Nedergaard and Goldman, \{Steven A.\}",

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doi = "10.1016/j.stem.2013.04.014",

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T1 - Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease

AU - Benraiss, Abdellatif

AU - Toner, Michael J.

AU - Xu, Qiwu

AU - Bruel-Jungerman, Elodie

AU - Rogers, Eloise H.

AU - Wang, Fushun

AU - Economides, Aris N.

AU - Davidson, Beverly L.

AU - Kageyama, Ryoichiro

AU - Nedergaard, Maiken

AU - Goldman, Steven A.

PY - 2013/6/6

Y1 - 2013/6/6

N2 - 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.

AB - 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.

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Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of huntington's disease

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