Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults

The study of the intracellular oxido-reductive (redox) state is of extremerelevance to the dopamine (DA) neurons of the substantia nigra pars compacta(SNpc). These cells posses a distinct physiology intrinsically associated withelevated ROS production, and they selectively degenerate in Parkinson’sdisease (PD) under oxidative stress conditions. We developed a new imagingstrategy to study redox variations in single cells that is sensitive enough to detectchanges within the physiological range. We studied DA neurons’ physiologicalredox response in biological systems of increasing complexity--from primarycultures to zebrafish larvae, to mammalian brains--and identified a redoxresponse that is distinctive for SNpc DA neurons. We studied simultaneously,and in the same cells, redox state and signaling activation, and found that thesephenomena are synchronized. While the new technique is of general interest,these findings provide insights into the biology of DA neurons in health anddisease, and may have implications for therapeutic intervention.