Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson's disease.
Direct intracerebral gene transfer to neural cells has been demonstrated with recombinant adenovirus encoding beta-galactosidase. To explore the potential of recombinant adenovirus for the therapy of neurological disease we constructed a recombinant adenovirus encoding tyrosine hydroxylase and optimized intracerebral injection to express the gene in the striatum of unilaterally denervated rats. These animals have dopamine depletion in their lesioned striatum, causing a rotation asymmetry induced by apomorphine. One and two weeks after intracerebral injection this sensorimotor asymmetry was decreased by the adenovirus encoding tyrosine hydroxylase and not by a control adenovirus encoding beta-galactosidase. Histological analysis showed that tyrosine hydroxylase was preferentially expressed in astrocytes.
Horellou
P
P
C 9923 CNRS, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Dégénératifs, Gif-sur-Yvette, France.
Vigne
E
E
Castel
M N
MN
Barnéoud
P
P
Colin
P
P
Perricaudet
M
M
Delaère
P
P
Mallet
J
J
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects; D003714:Denervation; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic; D013239:Stereotyped Behavior; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001616:beta-Galactosidase; D001058:Apomorphine