Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson's disease

被引：123

作者：

Sun, M ^{[1
]}

Kong, LX ^{[1
]}

Wang, XD ^{[1
]}

Lu, XG ^{[1
]}

Gao, QS ^{[1
]}

Geller, AI ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, W Roxbury VA Hosp, Dept Neurol, W Roxbury, MA 02132 USA

来源：

BRAIN RESEARCH | 2005年 / 1052卷 / 02期

关键词：

Parkinson's disease; gene therapy; glial cell line-derived neurotrophic factor; brain-derived neurotrophic factor; helper virus-free HSV-1 vector; neurodegeneration;

D O I：

10.1016/j.brainres.2005.05.072

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Both glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) can protect nigrostriatal dopaminergic neurons from neurotoxins in rodent and monkey models of Parkinson's disease (PD). These two neurotrophic factors are usually tested individually. This study was designed to compare GDNF, BDNF, or both, for their capabilities to correct behavioral deficits and protect nigrostriatal dopaminergic neurons in a rat model of PD. Gene transfer used a helper virus-free Herpes Simplex Virus (HSV-1) vector system and a modified neurofilament heavy gene promoter that supports long-term expression in forebrain neurons. Rats received unilateral intrastriatal injections of HSV-1 vectors that express either GDNF or BDNF, or both vectors, followed by intrastriatal injections of 6-hydroxydopamine (6-OHDA). Recombinant GDNF or BDNF was detected in striatal neurons in rats sacrificed at 7 months after gene transfer. Of note, GDNF was significantly more effective than BDNF for both correcting behavioral deficits and protecting nigrostriatal dopaminergic neurons. Expression of both neurotrophic factors was no more effective than expression of only GDNF. These results suggest that GDNF is more effective than BDNF for correcting the rat model of PD, and that there are no detectable benefits from expressing both of these neurotrophic factors. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：119 / 129

页数：11

共 44 条

[21] Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer [J].

Klein, RL ;

Lewis, MH ;

Muzyczka, N ;

Meyer, EM .

BRAIN RESEARCH, 1999, 847 (02) :314-320

[22] Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease [J].

Kordower, JH ;

Emborg, ME ;

Bloch, J ;

Ma, SY ;

Chu, YP ;

Leventhal, L ;

McBride, J ;

Chen, EY ;

Palfi, S ;

Roitberg, BZ ;

Brown, WD ;

Holden, JE ;

Pyzalski, R ;

Taylor, MD ;

Carvey, P ;

Ling, ZD ;

Trono, D ;

Hantraye, P ;

Déglon, N ;

Aebischer, P .

SCIENCE, 2000, 290 (5492) :767-773

[23] In vivo gene delivery of glial cell line-derived neurotrophic factor for Parkinson's disease [J].

Kordower, JH .

ANNALS OF NEUROLOGY, 2003, 53 :S120-S132

[24] Lentiviral gene transfer to the nonhuman primate brain [J].

Kordower, JH ;

Bloch, J ;

Ma, SY ;

Chu, YP ;

Palfi, S ;

Roitberg, BZ ;

Emborg, M ;

Hantraye, P ;

Déglon, N ;

Aebischer, P .

EXPERIMENTAL NEUROLOGY, 1999, 160 (01) :1-16

[25] Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease [J].

Levivier, M ;

Przedborski, S ;

Bencsics, C ;

Kang, UJ .

JOURNAL OF NEUROSCIENCE, 1995, 15 (12) :7810-7820

[26]

Lim F, 1996, BIOTECHNIQUES, V20, P460

[27] GDNF - A GLIAL-CELL LINE DERIVED NEUROTROPHIC FACTOR FOR MIDBRAIN DOPAMINERGIC-NEURONS [J].

LIN, LFH ;

DOHERTY, DH ;

LILE, JD ;

BEKTESH, S ;

COLLINS, F .

SCIENCE, 1993, 260 (5111) :1130-1132

[28]

Maniatis T., 1989, MOL CLONING

[29]

MOFFAT M, 1997, J NEUROCHEM, V68, P1792

[30]

MULLEN RJ, 1992, DEVELOPMENT, V116, P201

← 1 2 3 4 5 →