Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

Csaba Cserép; Balázs Pósfai; Nikolett Lénárt; Rebeka Fekete; Zsófia I. László; Zsolt Lele; Barbara Orsolits; Gábor Molnár; Steffanie Heindl; Anett D. Schwarcz; Katinka Ujvári; Zsuzsanna Környei; Krisztina Tóth; Eszter Szabadits; Beáta Sperlágh; Mária Baranyi; László Csiba; Tibor Hortobágyi; Zsófia Maglóczky; Bernadett Martinecz; Gábor Szabó; Ferenc Erdélyi; R. Szipöcs; Michael M. Tamkun; Benno G. Gesierich; Marco Duering; István Katona; Arthur Liesz; Gábor Tamás; Ádám Dénes

doi:10.1126/science.aax6752

NeuroscienceScienceDec 12, 2019

Peer-reviewed journal article

Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

Csaba Cserép iD, Balázs Pósfai iD, Nikolett Lénárt iD, Rebeka Fekete iD, Zsófia I. László iD, Zsolt Lele iD, Barbara Orsolits iD, Gábor Molnár iD, Steffanie Heindl iD, Anett D. Schwarcz iD, Katinka Ujvári, Zsuzsanna Környei iD, Krisztina Tóth iD, Eszter Szabadits iD, Beáta Sperlágh iD, Mária Baranyi iD, László Csiba iD, Tibor Hortobágyi iD, Zsófia Maglóczky iD, Bernadett Martinecz iD, Gábor Szabó iD, Ferenc Erdélyi iD, R. Szipöcs iD, Michael M. Tamkun iD, Benno G. Gesierich iD, , Ádám Dénes iD

Abstract

Microglia are the main immune cells in the brain with emerging roles in brain homeostasis and neurological diseases, while mechanisms underlying microglia-neuron communication remain elusive. Here, we identify a novel site of interaction between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia-neuron junctions possess specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria is linked with microglial junction formation, which is rapidly induced in response to neuronal activation and blocked by inhibition of P2Y12-receptors (P2Y12R). Brain injury-induced changes at somatic junctions trigger P2Y12R-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Collectively, our results suggest that microglial processes at these junctions are in ideal position to monitor and protect neuronal functions in both the healthy and injured brain.\n\nOne-sentence summaryNeuronal cell bodies possess specialized, pre-formed sites, through which microglia monitor their status and exert neuroprotection.

PDF DOI