LONG-TERM BEHAVIORAL RECOVERY IN PARKINSONIAN RATS BY AN HSV VECTOR EXPRESSING TYROSINE-HYDROXYLASE

被引:306
作者
DURING, MJ
NAEGELE, JR
OMALLEY, KL
GELLER, AI
机构
[1] YALE UNIV, SCH MED, DEPT MED, NEW HAVEN, CT 06510 USA
[2] WESLEYAN UNIV, DEPT BIOL, MIDDLETOWN, CT 06457 USA
[3] WASHINGTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, ST LOUIS, MO 63110 USA
[4] HARVARD UNIV, CHILDRENS HOSP, SCH MED, DIV ENDOCRINOL, BOSTON, MA 02115 USA
[5] HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA
关键词
D O I
10.1126/science.266.5189.1399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One therapeutic approach to treating Parkinson's disease is to convert endogenous striatal cells into levo-3,4-dihydroxyphenylalanine (L-dopa)-producing cells. A defective herpes simplex virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially denervated striatum of 6-hydroxydopamine-lesioned rats, used as a model of Parkinson's disease. Efficient behavioral and biochemical recovery was maintained for 1 year after gene transfer. Biochemical recovery included increases in both striatal tyrosine hydroxylase enzyme activity and in extracellular dopamine concentrations. Persistence of human tyrosine hydroxylase was revealed by expression of RNA and immunoreactivity.
引用
收藏
页码:1399 / 1403
页数:5
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