TY - JOUR
T1 - Astrocyte-originated ATP protects Aβ 1-42-induced impairment of synaptic plasticity
AU - Jung, Eun Sun
AU - An, Kyongman
AU - Hong, Hyun Seok
AU - Kim, Joung Hun
AU - Mook-Jung, Inhee
PY - 2012/2/29
Y1 - 2012/2/29
N2 - 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 byβ-amyloid peptide (Aβ). We found that Aβ 1-42 (Aβ42) increased the release of ATP in cultures of primary astrocytes and U373 astrocyte cell line. We also found that exogenous ATP protected Aβ42-mediated reduction in synaptic molecules, such as NMDA receptor 2A and PSD-95, through P2 purinergic receptors and prevented Aβ42-induced spine reduction in cultured primary hippocampal neurons. Moreover, ATP prevented Aβ42-induced impairment of long-term potentiation in acute hippocampal slices. Our findings suggest that Aβ-induced release of gliotransmitter ATP plays a protective role against Aβ42-mediated disruption of synaptic plasticity.
AB - 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 byβ-amyloid peptide (Aβ). We found that Aβ 1-42 (Aβ42) increased the release of ATP in cultures of primary astrocytes and U373 astrocyte cell line. We also found that exogenous ATP protected Aβ42-mediated reduction in synaptic molecules, such as NMDA receptor 2A and PSD-95, through P2 purinergic receptors and prevented Aβ42-induced spine reduction in cultured primary hippocampal neurons. Moreover, ATP prevented Aβ42-induced impairment of long-term potentiation in acute hippocampal slices. Our findings suggest that Aβ-induced release of gliotransmitter ATP plays a protective role against Aβ42-mediated disruption of synaptic plasticity.
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U2 - 10.1523/JNEUROSCI.6357-11.2012
DO - 10.1523/JNEUROSCI.6357-11.2012
M3 - Article
C2 - 22378880
AN - SCOPUS:84863282118
SN - 0270-6474
VL - 32
SP - 3081
EP - 3087
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 9
ER -