Ellagic acid supports neurons by regulating astroglia nuclear factor erythroid 2-related factor 2

OBJECTIVE Astroglia support neurons by providing substrates for neuronal metabolism, glutamate clearance and anti-oxidant protection. Nuclear factor erythroid 2-related factor 2(Nrf2) is the main switch of intracellular antioxidant defense system. Also, Nrf2 signaling is recognized to activate the neurotrophic pathway to replace/protect damaged organelles. Ellagic acid(EA), an excretion component of fruits and nuts, displays anti-oxidant, cardioprotective and antiinflammatory activities. However, few studies have been focused on the neurotrophic properties of EA. Our study investigated whether EA could enhance astroglia neurotrophic effects to support neurons and the underlying mechanisms as well. METHODS Primary neuron-enriched cultures, primary astroglia-enriched cultures and primary neuron-astroglia co-cultures were applied to detect whether pharmacological regulation of astroglia function by EA could be utilized to overcome neuronal death. RESULTS This study indicated that EA promoted neuronal survival. Furtherly, astroglia Nrf2 participate in EA-elicited neuronal survival with the following scenarios. First, EA induced astroglia proliferation, neurotrophic factors release and Nrf2 activation. Second, astroglia-targeted Nrf2 si RNA inhibited EA-mediated astrogliosis,neurotrophic factors excretion and neuronal survival. CONCLUSION EA mediated astroglia Nrf2 activation to enhanced neurotrophic effects on neurons, and these findings might provide new strategies for neurotrophic factor-based treatment of neurodegenerative disease.