Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF

被引：38

作者：

Emborg, M. E. ^{[1
,2
]}

Moirano, J. ^{[1
,2
]}

Raschke, J. ^{[1
]}

Bondarenko, V. ^{[1
]}

Zufferey, R. ^{[3
]}

Peng, S. ^{[1
]}

Ebert, A. D. ^{[4
]}

Joers, V. ^{[1
]}

Roitberg, B. ^{[5
]}

Holden, J. E. ^{[1
]}

Koprich, J. ^{[6
]}

Lipton, J. ^{[7
]}

Kordower, J. H. ^{[8
]}

Aebischer, P. ^{[4
]}

机构：

[1] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Preclin Parkinsons Res Program, Madison, WI 53715 USA

[2] Univ Wisconsin, Dept Med Phys, Madison, WI 53715 USA

[3] Univ Lausanne, CH-1015 Lausanne, Switzerland

[4] Univ Wisconsin, Waisman Ctr, Madison, WI 53715 USA

[5] Univ Illinois, Dept Neurosurg, Chicago, IL USA

[6] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada

[7] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA

[8] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA

来源：

NEUROBIOLOGY OF DISEASE | 2009年 / 36卷 / 02期

关键词：

Macaque; MPTP; GDNF; Gene transfer; Parkinson's disease; Aging; NIGROSTRIATAL DOPAMINE SYSTEM; RHESUS-MONKEYS; NEUROTROPHIC FACTOR; NONHUMAN-PRIMATES; SUBSTANTIA-NIGRA; PARS COMPACTA; 6-OHDA LESION; DISEASE; DELIVERY; MPTP;

D O I：

10.1016/j.nbd.2009.07.022

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-lacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：303 / 311

页数：9

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