Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.
Szentágothai János Doctoral School of Neuroscience, Semmelweis University, Budapest, Hungary.
Science. 2020 Jan 31;367(6477):528-537. doi: 10.1126/science.aax6752. Epub 2019 Dec 12.
Microglia are the main immune cells in the brain and have roles in brain homeostasis and neurological diseases. Mechanisms underlying microglia-neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia-neuron junctions have a specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria was linked with microglial junction formation, which was induced rapidly in response to neuronal activation and blocked by inhibition of P2Y12 receptors. Brain injury-induced changes at somatic junctions triggered P2Y12 receptor-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Thus, microglial processes at these junctions could potentially monitor and protect neuronal functions.
小胶质细胞是大脑中的主要免疫细胞，在大脑稳态和神经疾病中发挥作用。小胶质细胞-神经元通讯的机制仍不清楚。在这里，我们在小鼠和人类大脑中鉴定出神经元细胞体和小胶质细胞突起之间的相互作用位点。体细胞小胶质细胞-神经元连接具有优化的嘌呤能信号传递的特殊纳米结构。神经元线粒体的活性与小胶质细胞连接的形成有关，后者可快速响应神经元激活而被诱导，并可被 P2Y12 受体抑制所阻断。脑损伤引起的体细胞连接变化触发 P2Y12 受体依赖性小胶质细胞神经保护作用，调节神经元钙负荷和功能连接。因此，这些连接点处的小胶质细胞突起可能潜在地监测和保护神经元功能。
