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AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model.

Abstract：

:Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with progressive pathology involving the loss of midbrain dopaminergic neurons. Neurotrophic factors are promising for PD gene therapy; they are integrally involved in the development of the nigrostriatal system. Cerebral dopamine neurotrophic factor (CDNF) was recently discovered to be more selective and potent on preserving dopaminergic neurons than other known trophic factors. The present study examined the neuroprotective and functional restorative effects of CDNF overexpression in the striatum via recombinant adeno-associated virus type 2 (AAV2.CDNF) in 6-hydroxydopamine (6-OHDA) injected rats. Striatal delivery of AAV2.CDNF was able to recover 6-OHDA-induced behavior deficits and resulted in a significant restoration of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and TH-ir fiber density in the striatum. PET analyses with [(11)C]-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ([(11)C]β-CFT) probes suggested functional recovery of dopaminergic (DA) neurons. Our results indicate that striatal administration of AAV2.CDNF was able to provide effective neuro-restoration in the 6-OHDA-lesioned nigrostriatal system and that it may be considered for future clinical applications in PD therapy.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Ren X,Zhang T,Gong X,Hu G,Ding W,Wang X

doi

10.1016/j.expneurol.2013.06.002

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

148-56

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(13)00174-X

journal_volume

248

pub_type

杂志文章

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