第64回日本神経病理学会総会学術研究会 第66回日本神経化学会大会 合同大会
鈴木 秀明さん
第64回日本神経病理学会総会学術研究会/第66回日本神経化学会大会 合同大会 参加報告
薬理学教室 鈴木秀明
この度はライフサイエンスコースのサポートを受け神戸国際会議場にて開催された第66回日本神経化学会大会でポスター発表をさせていただきました。現地対面開催の学会であり自身の発表内容に関して他大学の先生方と直接ディスカッションすることができ、また、多様な演題に触れることができた貴重な機会でした。
以下に発表の抄録を示す。
ATP acts as a signaling molecule involved in neurotransmission and neuron-glia signaling and is known to be involved in psychiatric disorders such as depression and neurological disorders such as chronic pain. Although ATP has been shown to be released by multiple types of cells in the CNS, it remains unknown how and from which cells ATP is released under physiological conditions due to the lack of a method to detect the spatiotemporal dynamics of extracellular ATP with high sensitivity. To understand the ATP dynamics, we imaged astrocyte extracellular ATP signal using a genetically encoded G protein-coupled receptor activation-based ATP sensor called GRABATP1.0 in the CA1 region of acute hippocampal slices. Electrical stimulation of the Schaffer collateral resulted in ATP rise extracellularly in astrocytes, and this response increased in a stimulus-dependent manner. The response was inhibited by TTX, but still remained in the presence of D-APV/CNQX. These data suggest that the source of activity-dependent ATP release could be presynaptic sites rather than postsynaptic sites of neurons. Depletion of microglia by treatment with PLX5622 prolonged the duration of ATP signal, suggesting that microglia, which highly express NTPDase1, rapidly degrade ATP to terminate ATP signaling. We found comparable ATP responses occurred in IP3 receptor type 2 knock-out mouse model as the wild type mice, suggesting that IP3R2-signaling in astrocytes has a relatively small contribution to the ATP responses. Overall data show that neuronal activity induces ATP release from axons or axon terminals and its ATP is subsequently negatively regulated by microglia in physiology.
