Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson's disease.
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.
Sun
Mei
M
Department of Neurology, W. Roxbury V.A. Hospital/Harvard Medical School, MA 02132, USA.
Kong
Lingxin
L
Wang
Xiaodan
X
Lu
Xiu-gui
XG
Gao
Qingsheng
Q
Geller
Alfred I
AI
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D002460:Cell Line; D003342:Corpus Striatum / Q000473:pathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007839:Functional Laterality; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry / Q000379:methods; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000209:etiology / Q000628:therapy; D051381:Rats; D012399:Rotation; D018139:Simplexvirus / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology*
D018663:Adrenergic Agents; D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine; D001058:Apomorphine