Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease

被引：76

作者：

Back, Susanne ^{[1
]}

Peranen, Johan ^{[2
]}

Galli, Emilia ^{[2
,3
]}

Pulkkila, Paivi ^{[2
]}

Lonka-Nevalaita, Liina ^{[2
]}

Tamminen, Tuulia ^{[1
]}

Voutilainen, Merja H. ^{[1
]}

Raasmaja, Atso ^{[1
]}

Saarma, Mart ^{[2
]}

Mannisto, Pekka T. ^{[1
]}

Tuominen, Raimo K. ^{[1
]}

机构：

[1] Univ Helsinki, Fac Pharm, Div Pharmacol & Toxicol, FIN-00014 Helsinki, Finland

[2] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Fac Pharm, Div Biopharmaceut & Pharmacokinet, FIN-00014 Helsinki, Finland

来源：

BRAIN AND BEHAVIOR | 2013年 / 3卷 / 02期

基金：

芬兰科学院;

关键词：

6-OHDA; AAV; CDNF; GDNF; gene therapy; NEUROTROPHIC FACTOR; NIGROSTRIATAL SYSTEM; STRIATAL DELIVERY; DOPAMINE NEURONS; DOUBLE-BLIND; HUMAN NEURTURIN; CDNF PROTECTS; AAV2; VECTOR; OPEN-LABEL; GDNF;

D O I：

10.1002/brb3.117

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Cerebral dopamine neurotrophic factor (CDNF) protein has been shown to protect the nigrostriatal dopaminergic pathway when given as intrastriatal infusions in rat and mouse models of Parkinson's disease (PD). In this study, we assessed the neuroprotective effect of CDNF delivered with a recombinant adeno-associated viral (AAV) serotype 2 vector in a rat 6-hydroxydopamine (6-OHDA) model of PD. AAV2 vectors encoding CDNF, glial cell line-derived neurotrophic factor (GDNF), or green fluorescent protein were injected into the rat striatum. Protein expression analysis showed that our AAV2 vector efficiently delivered the neurotrophic factor genes into the brain and gave rise to a long-lasting expression of the proteins. Two weeks after AAV2 vector injection, 6-OHDA was injected into the rat striatum, creating a progressive degeneration of the nigrostriatal dopaminergic system. Treatment with AAV2-CDNF resulted in a marked decrease in amphetamine-induced ipsilateral rotations while it provided only partial protection of tyrosine hydroxylase (TH)-immunoreactive cells in the rat substantia nigra pars compacta and TH-reactive fibers in the striatum. Results from this study provide additional evidence that CDNF can be considered a potential treatment of Parkinson's disease.

引用

页码：75 / 88

页数：14

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