Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice

被引:109
作者
Szczypka, MS
Mandel, RJ
Donahue, BA
Snyder, RO
Leff, SE
Palmiter, RD [1 ]
机构
[1] Univ Washington, Howard Hughes Med Inst, Dept Biochem, Seattle, WA 98195 USA
[2] Cell Genesys Inc, Dept Preclin Biol, Foster City, CA 94404 USA
关键词
D O I
10.1016/S0896-6273(00)80688-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dopamine-deficient mice (DA(-/-)), lacking tyrosine hydroxylase (TH) in dopaminergic neurons, become hypoactive and aphagic and die by 4 weeks of age. They are rescued by daily treatment with LB, Q-dihydroxyphenylalanine (L-DOPA); each dose restores dopamine (DA) and feeding for less than 24 hr. Recombinant adeno-associated viruses expressing human TH or GTP cyclohydrolase 1 (GTPCH1) were injected into the striatum of DA(-/-) mice. Bilateral coinjection of both viruses restored feeding behavior for several months. However, locomotor activity and coordination were partially improved. A virus expressing only TH was less effective, and one expressing GTPCH1 alone was ineffective. TH immunoreactivity and DA were detected in the ventral striatum and adjacent posterior regions of rescued mice, suggesting that these regions mediate a critical DA-dependent aspect of feeding behavior.
引用
收藏
页码:167 / 178
页数:12
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