DIRECT INTRACEREBRAL GENE-TRANSFER OF AN ADENOVIRAL VECTOR EXPRESSING TYROSINE-HYDROXYLASE IN A RAT MODEL OF PARKINSONS-DISEASE

被引:141
作者
HORELLOU, P
VIGNE, E
CASTEL, MN
BARNEOUD, P
COLIN, P
PERRICAUDET, M
DELAERE, P
MALLET, J
机构
[1] CNRS,GENET MOLEC NEUROTRANSMISS & PROC DEGENERATIFS LA,C 9923,F-91198 GIF SUR YVETTE,FRANCE
[2] INST GUSTAVE ROUSSY,CNRS,URA 1301,PR2,F-94805 VILLEJUIF,FRANCE
[3] RHONE POULENC RORER,CTR RECH VITRY ALFORTVILLE,F-94403 VITRY,FRANCE
关键词
TYROSINE HYDROXYLASE; PARKINSONS DISEASE; RECOMBINANT ADENOVIRUS; STRIATUM; 6-HYDROXYDOPAMINE; INTRACEREBRAL INJECTION; APOMORPHINE-INDUCED ROTATION; IN VIVO GENE THERAPY;
D O I
10.1097/00001756-199412300-00014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 tl;is 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.
引用
收藏
页码:49 / 53
页数:5
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