Astrocyte-Originated ATP Protects A beta(1-42)-Induced Impairment of Synaptic Plasticity

Abstract

Activated microglia and reactive astrocytes are commonly found in and around the senile plaque, which is the central pathological hallmark of Alzheimer's disease. Astrocytes respond to neuronal activity through the release of gliotransmitters such as glutamate, D-serine, and ATP. However, it is largely unknown whether and how gliotransmitters affect neuronal functions. In this study, we explored the effect of a gliotransmitter, ATP, on neurons damaged by beta-amyloid peptide (A beta). We found that A beta(1-42) (A beta 42) increased the release of ATP in cultures of primary astrocytes and U373 astrocyte cell line. We also found that exogenous ATP protected A beta 42-mediated reduction in synaptic molecules, such as NMDA receptor 2A and PSD-95, through P2 purinergic receptors and prevented A beta 42-induced spine reduction in cultured primary hippocampal neurons. Moreover, ATP prevented A beta 42-induced impairment of long-term potentiation in acute hippocampal slices. Our findings suggest that A beta-induced release of gliotransmitter ATP plays a protective role against A beta 42-mediated disruption of synaptic plasticity.