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首页> 外文期刊>Neuron >Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice.
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Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice.

机译:病毒基因的传递选择性地恢复了喂养,并防止了多巴胺缺乏小鼠的致死性。

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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 L-3,4-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.
机译:在多巴胺能神经元中缺乏酪氨酸羟化酶(TH)的多巴胺缺陷小鼠(DA-/-)变得机能亢进,失语,并在4周龄时死亡。通过每天用L-3,4-二羟基苯丙氨酸(L-DOPA)进行治疗可以拯救它们;每次剂量可恢复多巴胺(DA),并且喂养时间少于24小时。将表达人TH或GTP环水解酶1(GTPCH1)的重组腺相关病毒注射到DA-/-小鼠的纹状体中。两种病毒的双向共注射恢复了几个月的进食行为。但是,运动活动和协调能力得到了部分改善。仅表达TH的病毒效果较差,仅表达GTPCH1的病毒无效。在被拯救小鼠的腹侧纹状体和邻近的后部区域检测到TH免疫反应性和DA,表明这些区域介导了喂养行为的关键的DA依赖性方面。

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