title: Astrocyte-originated ATP protects Aβ(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 β-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.
authors.affiliation: Department of Biochemistry and Biomedical Science, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jung
authors.forename: Kyongman
authors.initials: K
authors.lastname: An
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Hong
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity / Q000502:physiology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000255:Adenosine Triphosphate