Abstract
Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson's disease-linked protein DJ-1β as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.
Highlights
Levels of reactive oxygen species (ROS) in the brain increase with ageing and high levels of ROS are a hallmark of neurodegeneration, including Alzheimer’s and Parkinson’s disease (Hohn and Grune, 2013; Martins et al, 1986; Spina and Cohen, 1989) for review see (Milton and Sweeney, 2012)
Structural plasticity of synaptic terminals is regulated by neuronal activity Our aim was to explore roles for activity-regulated ROS signaling in the nervous system under nonpathological conditions
Activity-regulated changes in miniature excitatory junction potentials (mEJPs) amplitude depend on ROS signaling, though this is not impacted by the over-expression of cytoplasmic Catalase; instead we found this aspect of synaptic transmission sensitive to oxidation of DJ-1b
Summary
Levels of reactive oxygen species (ROS) in the brain increase with ageing and high levels of ROS are a hallmark of neurodegeneration, including Alzheimer’s and Parkinson’s disease (Hohn and Grune, 2013; Martins et al, 1986; Spina and Cohen, 1989) for review see (Milton and Sweeney, 2012). Mitochondria are a significant source of ROS, which form as obligate byproducts of respiratory ATP synthesis by ‘leakage’ of the electron transport chain, leading to the generation of superoxide anions (O2-) and hydrogen peroxide (H2O2) (Halliwell, 1992). Implicit in their name, ROS are highly reactive, containing one or more unpaired electrons, with the potential to modify and damage by oxidation proteins, lipids and DNA (Gladyshev, 2014; Harman, 1956; Stuart et al, 2014).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
