These authors contributed equally to this study.
Selective degeneration of dopaminergic neurons by MPP+ and its rescue by D2 autoreceptors in Drosophila primary culture
Article first published online: 24 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 4, pages 529–540, August 2013
How to Cite
J. Neurochem. (2013) 126, 529–540.
- Issue published online: 5 AUG 2013
- Article first published online: 24 MAR 2013
- Accepted manuscript online: 1 MAR 2013 12:55PM EST
- Manuscript Accepted: 14 FEB 2013
- Manuscript Revised: 10 JAN 2013
- Manuscript Received: 11 SEP 2012
- NIH. Grant Number: NS050260
- Korea Institute of Science & Technology (Brain Science Institute), Seoul, Korea
- D2 agonist;
- Drosophila melanogaster ;
- Parkinson's disease;
- primary neuronal culture
Drosophila melanogaster is widely used to study genetic factors causing Parkinson's disease (PD) largely because of 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+. Dopaminergic (DA) neurons were selectively degenerated by MPP+, whereas cholinergic and GABAergic neurons were not affected. This DA neuronal loss was because of 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.