PT  - JOURNAL ARTICLE
AU  - Jun Wu
AU  - J. Deborah Holstein
AU  - Geeta Upadhyay
AU  - Da-Ting Lin
AU  - Stuart Conway
AU  - Elizabeth Muller
AU  - James D. Lechleiter
TI  - Purinergic Receptor-Stimulated IP<sub>3</sub>-Mediated Ca<sup>2+</sup> Release Enhances Neuroprotection by Increasing Astrocyte Mitochondrial Metabolism during Aging
AID  - 10.1523/JNEUROSCI.1256-07.2007
DP  - 2007 Jun 13
TA  - The Journal of Neuroscience
PG  - 6510--6520
VI  - 27
IP  - 24
4099  - http://www.jneurosci.org/content/27/24/6510.short
4100  - http://www.jneurosci.org/content/27/24/6510.full
SO  - J. Neurosci.2007 Jun 13; 27
AB  - Astrocytes play an essential role in the maintenance and protection of the brain, which we reported was diminished with age. Here, we demonstrate that activation of a purinergic receptor (P2Y-R) signaling pathway, in astrocytes, significantly increases the resistance of astrocytes and neurons to oxidative stress. Interestingly, P2Y-R activation in old astrocytes increased their resistance to oxidative stress to levels that were comparable with stimulated young astrocytes. P2Y-R enhanced neuroprotection was blocked by oligomycin and by Xestospongin C, inhibitors of the ATP synthase and of inositol (1,4,5) triphosphate (IP3) binding to the IP3 receptor, respectively. Treatment of astrocytes with a membrane permeant analog of IP3 also protected astrocytes against oxidative stress. These data indicate that P2Y-R enhanced astrocyte neuroprotection is mediated by a Ca2+-dependent increase in mitochondrial metabolism. These data also reveal a signaling pathway that can rapidly respond to central energy needs throughout the aging process.