New paper in Science by KOKI researchers, using STORM super-resolution imaging: “Microglia monitor and protect neuronal function via specialized somatic purinergic junctions”

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Microglia are the main immune cells in the brain with 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 possessed 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 (P2Y12R). Brain injury-induced changes at somatic junctions triggered P2Y12R-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Thus, microglial processes at these junctions could potentially monitor and protect neuronal functions.

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Csaba Cserép1,*, Balázs Pósfai1,2,*, Nikolett Lénárt1, Rebeka Fekete1,2, Zsófia I. László2,3, Zsolt Lele3, Barbara Orsolits1, Gábor Molnár4, Steffanie Heindl5, Anett D. Schwarcz1, Katinka Ujvári1, Zsuzsanna Környei1, Krisztina Tóth1,2, Eszter Szabadits1, Beáta Sperlágh6, Mária Baranyi6, László Csiba7, Tibor Hortobágyi8,9,10, Zsófia Maglóczky11, Bernadett Martinecz1, Gábor Szabó12, Ferenc Erdélyi12, Róbert Szipőcs13, Michael M. Tamkun14, Benno Gesierich5, Marco Duering5,15, István Katona3, Arthur Liesz5,15, Gábor Tamás4, Ádám Dénes1,

1“Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.

2Szentágothai János Doctoral School of Neuroscience, Semmelweis University, Budapest, Hungary.

3“Momentum” Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.

4MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.

5Institute for Stroke and Dementia Research, Ludwig-Maximilians-University, Munich, Germany.

6Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Budapest, Hungary.

7MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary.

8Institute of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary.

9Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.

10Centre for Age-Related Medicine, SESAM, Stavanger University Hospital, Stavanger, Norway.

11Human Brain Research Laboratory, Institute of Experimental Medicine, Budapest, Hungary.

12Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.

13Institute for Solid State Physics and Optics of Wigner RCP, Budapest, Hungary.

14Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.

15Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.