Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

• Published in: Science (American Association for the Advancement of Science) Vol. 367; no. 6477; pp. 528 - 537
• Main Authors: Cserép, Csaba, Pósfai, Balázs, Lénárt, Nikolett, Fekete, Rebeka, László, Zsófia I., Lele, Zsolt, Orsolits, Barbara, Molnár, Gábor, Heindl, Steffanie, Schwarcz, Anett D., Ujvári, Katinka, Környei, Zsuzsanna, Tóth, Krisztina, Szabadits, Eszter, Sperlágh, Beáta, Baranyi, Mária, Csiba, László, Hortobágyi, Tibor, Maglóczky, Zsófia, Martinecz, Bernadett, Szabó, Gábor, Erdélyi, Ferenc, Szipőcs, Róbert, Tamkun, Michael M., Gesierich, Benno, Duering, Marco, Katona, István, Liesz, Arthur, Tamás, Gábor, Dénes, Ádám
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 31.01.2020
• Subjects: Anatomy; Animals; Brain; Brain - immunology; Brain - ultrastructure; Brain Injuries - immunology; Brain Injuries - pathology; Calcium; Cell Communication - immunology; Central nervous system; Chemical composition; Communication; Epilepsy; Head injuries; HEK293 Cells; Homeostasis; Humans; Immune system; Intercellular Junctions - immunology; Mental disorders; Mice; Microglia; Microglia - immunology; Mitochondria; Mitochondria - immunology; Neurological diseases; Neurons - immunology; Receptors; Receptors, Purinergic P2Y12 - physiology; Shab Potassium Channels - genetics; Shab Potassium Channels - physiology; Signal Transduction; Signaling; Traumatic brain injury
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aax6752

Changes in the activity of microglia, the primary immune cells of the central nervous system, are linked with major human diseases, including stroke, epilepsy, psychiatric disorders, and neurodegeneration. Cserép et al. identified a specialized morphofunctional communication site between microglial processes and neuronal cell bodies in the mouse and the human brain (see the Perspective by Nimmerjahn). These junctions are formed at specific areas of the neuronal somatic membranes and possess a distinctive nanoarchitecture and specialized molecular composition linked to mitochondrial signaling. The junctions appear to provide a major site for microglia-neuron communication and may help to mediate the neuroprotective effects of microglia after acute brain injury. Science , this issue p. 528 ; see also p. 510 Neuronal somata possess specialized, preformed sites through which microglia monitor their status and exert neuroprotection. 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.