Astrocyte NMDA receptors' activity sustains neuronal survival through a Cdk5-Nrf2 pathway.

ABSTRACT: Neurotransmission unavoidably increases mitochondrial reactive oxygen species. However, the intrinsic antioxidant defense of neurons is weak and hence the mechanism whereby these cells are physiologically protected against oxidative damage is unknown. Here we found that the antioxidant defense of neurons is repressed owing to the continuous protein destabilization of the master antioxidant transcriptional activator, nuclear factor-erythroid 2-related factor-2 (Nrf2). By contrast, Nrf2 is highly stable in neighbor astrocytes explaining their robust antioxidant defense and resistance against oxidative stress. We also show that subtle and persistent stimulation of N-methyl-d-aspartate receptors (NMDAR) in astrocytes, through a mechanism not requiring extracellular Ca²⁺ influx, upregulates a s

SUBMITTER: Jimenez-Blasco D 

PROVIDER: S-EPMC4648333 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature