Open AccessGene therapy with AAV 2‐ CDNF provides functional benefits in a rat model of P arkinson's disease
Author(s) -
Bäck Susanne,
Peränen Johan,
Galli Emilia,
Pulkkila Päivi,
LonkaNevalaita Liina,
Tamminen Tuulia,
Voutilainen Merja H.,
Raasmaja Atso,
Saarma Mart,
Männistö Pekka T.,
Tuominen Raimo K.
Publication year - 2013
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.117
Subject(s) - glial cell line derived neurotrophic factor , tyrosine hydroxylase , substantia nigra , neurotrophic factors , dopaminergic , striatum , pars compacta , dopamine , biology , neuroprotection , nigrostriatal pathway , neurotrophin , pharmacology , endocrinology , biochemistry , receptor
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 P arkinson'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 . AAV 2 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 AAV 2 vector efficiently delivered the neurotrophic factor genes into the brain and gave rise to a long‐lasting expression of the proteins. Two weeks after AAV 2 vector injection, 6‐ OHDA was injected into the rat striatum, creating a progressive degeneration of the nigrostriatal dopaminergic system. Treatment with AAV 2‐ 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 P arkinson's disease.