Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Csaba Cserép^#¹, Balázs Pósfai^#^{1 2}, Nikolett Lénárt¹, Rebeka Fekete^{1 2}, Zsófia I László^{2 3}, Zsolt Lele³, Barbara Orsolits¹, Gábor Molnár⁴, Steffanie Heindl⁵, Anett D Schwarcz¹, Katinka Ujvári¹, Zsuzsanna Környei¹, Krisztina Tóth^{1 2}, Eszter Szabadits¹, Beáta Sperlágh⁶, Mária Baranyi⁶, László Csiba⁷, Tibor Hortobágyi^{8 9 10}, Zsófia Maglóczky¹¹, Bernadett Martinecz¹, Gábor Szabó¹², Ferenc Erdélyi¹², Róbert Szipőcs¹³, Michael M Tamkun¹⁴, Benno Gesierich⁵, Marco Duering^{5 15}, István Katona³, Arthur Liesz^{5 15}, Gábor Tamás⁴, Ádám Dénes¹⁶

Affiliations

¹ Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.
² Szentágothai János Doctoral School of Neuroscience, Semmelweis University, Budapest, Hungary.
³ Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
⁴ MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.
⁵ Institute for Stroke and Dementia Research, Ludwig-Maximilians-University, Munich, Germany.
⁶ Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Budapest, Hungary.
⁷ MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary.
⁸ Institute of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
⁹ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁰ Centre for Age-Related Medicine, SESAM, Stavanger University Hospital, Stavanger, Norway.
¹¹ Human Brain Research Laboratory, Institute of Experimental Medicine, Budapest, Hungary.
¹² Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.
¹³ Institute for Solid State Physics and Optics of Wigner RCP, Budapest, Hungary.
¹⁴ Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
¹⁵ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁶ Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary. denes.adam@koki.mta.hu.

^# Contributed equally.

PMID:31831638
DOI: 10.1126/science.aax6752

Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Csaba Cserép et al. Science.2020.

.2020 Jan 31;367(6477):528-537.

doi: 10.1126/science.aax6752. Epub 2019 Dec 12.

Authors

Affiliations

¹ Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.
² Szentágothai János Doctoral School of Neuroscience, Semmelweis University, Budapest, Hungary.
³ Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
⁴ MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.
⁵ Institute for Stroke and Dementia Research, Ludwig-Maximilians-University, Munich, Germany.
⁶ Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Budapest, Hungary.
⁷ MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary.
⁸ Institute of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
⁹ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁰ Centre for Age-Related Medicine, SESAM, Stavanger University Hospital, Stavanger, Norway.
¹¹ Human Brain Research Laboratory, Institute of Experimental Medicine, Budapest, Hungary.
¹² Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.
¹³ Institute for Solid State Physics and Optics of Wigner RCP, Budapest, Hungary.
¹⁴ Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
¹⁵ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁶ Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary. denes.adam@koki.mta.hu.

^# Contributed equally.

PMID:31831638
DOI: 10.1126/science.aax6752

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.

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Monitoring neuronal health.
Nimmerjahn A.Nimmerjahn A.Science. 2020 Jan 31;367(6477):510-511. doi: 10.1126/science.aba4472.Science. 2020.PMID:32001643Free PMC article.No abstract available.

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Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

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Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

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