Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Cserép, C.; Pósfai, B.; Lénárt, N.; Fekete, R.; László, Z. I.; Lele, Z.; Orsolits, B.; Molnár, G.; Heindl, S.; Schwarcz, A. D.; Ujvári, K.; Környei, Z.; Tóth, K.; Szabadits, E.; Sperlágh, B.; Baranyi, M.; Csiba, L.; Hortobágyi, T.; Maglóczky, Z.; Martinecz, B.; Szabó, G.; Erdélyi, F.; Szipőcs, R.; Tamkun, M. M.; Gesierich, B.; Duering, M.; Katona, I.; Liesz, Arthur; Tamás, G. und Dénes, Á. (2020): Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. In: Science, Bd. 367, Nr. 6477: S. 528-537

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 802305
• EU-Projekte: Horizon 2020 > ERC Grants > ERC Starting Grant > ERC Grant 802305: RecoverInFlame - T cell-driven inflammatory mechanisms promote recovery after acute brain injury
• Publikationsform: Postprint
• Fakultät: Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Bemerkung: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on Vol. 367, Issue 6477, 31 Jan 2020, DOI: 10.1126/science.aax6752
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198