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

作者：Jung Eun Sun; An Kyongman; Hong Hyun Seok; Kim Joung Hun; Mook Jung Inhee^*

来源：Journal of Neuroscience, 2012, 32(9): 3081-3087.

DOI：10.1523/JNEUROSCI.6357-11.2012

Activated microglia and reactive astrocytes are commonly found in and around the senile plaque, which is the central pathological hallmark of Alzheimer%26apos;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.

• 出版日期2012-2-29