ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor alpha (ERR alpha) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERR alpha on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERR alpha expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERR alpha. Additionally, we also found that knocking down ERR alpha expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERR alpha knockdown. These results indicate a new possible cellular mechanism by which ERR alpha affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.