Selective degeneration of dopaminergic neurons by MPP(+) and its rescue by D2 autoreceptors in Drosophila primary culture.
Selective degeneration of dopaminergic neurons by MPP(+) and its rescue by D2 autoreceptors in Drosophila primary culture.
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DOI：
10.1111/jnc.12228
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发表时间：
2013-08
影响因子：
4.7
通讯作者：
Lee D
中科院分区：
文献类型：
--
作者：
Wiemerslage L;Schultz BJ;Ganguly A;Lee D
黑腹果蝇被广泛用于研究导致帕金森病（PD）的遗传因素，这主要是由于复杂遗传方法的使用以及果蝇和哺乳动物之间基因序列/功能的高度保守性。然而，在果蝇中，很少有人研究导致90%以上PD病例的环境因素。我们使用果蝇原代神经元培养物来研究众所周知的PD毒素MPP+的退行性作用。MPP+使DA能神经元选择性变性，而对胆碱能和GABA能神经元无明显影响。这种DA神经元的损失是由于有丝分裂后变性，而不是通过抑制DA神经元分化。我们还发现，MPP+介导的神经退行性变被D2激动剂喹吡罗和溴隐亭拯救。这种拯救是通过激活果蝇D2受体DD 2 R，因为D2激动剂未能拯救从DD 2 R缺陷系和全神经元表达DD 2 R RNAi的转基因系制备的神经元培养物中的MPP+毒性。此外，DA神经元中的DD 2 R自身受体在拯救中发挥了关键作用。当DD 2 R RNAi仅在DA神经元中表达时，D2激动剂不能挽救MPP+毒性。我们的研究还表明，拯救DA神经元变性的果蝇DD 2 R激活介导的抑制DA神经元的动作电位。
Drosophila melanogaster is widely used to study genetic factors causing Parkinson’s disease (PD) due largely to the use of sophisticated genetic approaches and the presence of a high conservation of gene sequence/function between Drosophila and mammals. However, in Drosophila little has been done to study the environmental factors which cause over 90% of PD cases. We used Drosophila primary neuronal culture to study degenerative effects of a well-known PD toxin MPP+. DA neurons were selectively degenerated by MPP+ whereas cholinergic and GABAergic neurons were not affected. This DA neuronal loss was due to post-mitotic degeneration, not by inhibition of DA neuronal differentiation. We also found that MPP+-mediated neurodegeneration was rescued by D2 agonists quinpirole and bromocriptine. This rescue was through activation of Drosophila D2 receptor DD2R, as D2 agonists failed to rescue MPP+-toxicity in neuronal cultures prepared from both a DD2R deficiency line and a transgenic line pan-neuronally expressing DD2R RNAi. Furthermore, DD2R autoreceptors in DA neurons played a critical role in the rescue. When DD2R RNAi was expressed only in DA neurons, MPP+ toxicity was not rescued by D2 agonists. Our study also showed that rescue of DA neurodegeneration by Drosophila DD2R activation was mediated through suppression of action potentials in DA neurons.
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影响因子：
5
作者：
CARTER, AJ;MULLER, RE
通讯作者：
MULLER, RE
影响因子：
16.2
作者：
Han, KA;Millar, NS;Davis, RL
通讯作者：
Davis, RL
影响因子：
56.9
作者：
Auluck, PK;Chan, HYE;Bonini, NM
通讯作者：
Bonini, NM
DOI：
10.1073/pnas.97.4.1873
发表时间：
2000-02-15
影响因子：
11.1
作者：
Andretic, R;Hirsh, J
通讯作者：
Hirsh, J
影响因子：
3
作者：
Boone, Jason Q.;Doe, Chris Q.
通讯作者：
Doe, Chris Q.