Microglia monitor and protect neuronal function through 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; Róbert Szipocs; Michael M. Tamkun; Benno Gesierich; Marco Duering; István Katona; Arthur Liesz; Gábor Tamás; Ádám Dénes

doi:10.1126/science.aax6752

Microglia monitor and protect neuronal function through 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 MartineczGábor Szabó, Ferenc Erdélyi, Róbert Szipocs, Michael M. Tamkun, Benno Gesierich, Marco Duering, István Katona, Arthur Liesz, Gábor Tamás, Ádám Dénes

Systems Medicine

Research output: Contribution to journal › Article › peer-review

273 Citations (Scopus)

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.

Original language	English
Pages (from-to)	528-537
Number of pages	10
Journal	Science
Volume	367
Issue number	6477
DOIs	https://doi.org/10.1126/science.aax6752
Publication status	Published - 31 Jan 2020

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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., ... Dénes, Á. (2020). Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science, 367(6477), 528-537. https://doi.org/10.1126/science.aax6752

@article{cbfa96ab1a424d25a008ccfe9eafcb8a,

title = "Microglia monitor and protect neuronal function through specialized somatic purinergic junctions",

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.",

author = "Csaba Cser{\'e}p and Bal{\'a}zs P{\'o}sfai and Nikolett L{\'e}n{\'a}rt and Rebeka Fekete and L{\'a}szl{\'o}, {Zs{\'o}fia I.} and Zsolt Lele and Barbara Orsolits and G{\'a}bor Moln{\'a}r and Steffanie Heindl and Schwarcz, {Anett D.} and Katinka Ujv{\'a}ri and Zsuzsanna K{\"o}rnyei and Krisztina T{\'o}th and Eszter Szabadits and Be{\'a}ta Sperl{\'a}gh and M{\'a}ria Baranyi and L{\'a}szl{\'o} Csiba and Tibor Hortob{\'a}gyi and Zs{\'o}fia Magl{\'o}czky and Bernadett Martinecz and G{\'a}bor Szab{\'o} and Ferenc Erd{\'e}lyi and R{\'o}bert Szipocs and Tamkun, {Michael M.} and Benno Gesierich and Marco Duering and Istv{\'a}n Katona and Arthur Liesz and G{\'a}bor Tam{\'a}s and {\'A}d{\'a}m D{\'e}nes",

year = "2020",

month = jan,

day = "31",

doi = "10.1126/science.aax6752",

language = "English",

volume = "367",

pages = "528--537",

journal = "Science",

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Cserép, C, Pósfai, B, Lénárt, N, Fekete, R, László, ZI, Lele, Z, Orsolits, B, Molnár, G, Heindl, S, Schwarcz, AD, Ujvári, K, Környei, Z, Tóth, K, Szabadits, E, Sperlágh, B, Baranyi, M, Csiba, L, Hortobágyi, T, Maglóczky, Z, Martinecz, B, Szabó, G, Erdélyi, F, Szipocs, R, Tamkun, MM, Gesierich, B, Duering, M, Katona, I, Liesz, A, Tamás, G & Dénes, Á 2020, 'Microglia monitor and protect neuronal function through specialized somatic purinergic junctions', Science, vol. 367, no. 6477, pp. 528-537. https://doi.org/10.1126/science.aax6752

TY - JOUR

T1 - Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

AU - Cserép, Csaba

AU - Pósfai, Balázs

AU - Lénárt, Nikolett

AU - Fekete, Rebeka

AU - László, Zsófia I.

AU - Lele, Zsolt

AU - Orsolits, Barbara

AU - Molnár, Gábor

AU - Heindl, Steffanie

AU - Schwarcz, Anett D.

AU - Ujvári, Katinka

AU - Környei, Zsuzsanna

AU - Tóth, Krisztina

AU - Szabadits, Eszter

AU - Sperlágh, Beáta

AU - Baranyi, Mária

AU - Csiba, László

AU - Hortobágyi, Tibor

AU - Maglóczky, Zsófia

AU - Martinecz, Bernadett

AU - Szabó, Gábor

AU - Erdélyi, Ferenc

AU - Szipocs, Róbert

AU - Tamkun, Michael M.

AU - Gesierich, Benno

AU - Duering, Marco

AU - Katona, István

AU - Liesz, Arthur

AU - Tamás, Gábor

AU - Dénes, Ádám

PY - 2020/1/31

Y1 - 2020/1/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85078742646&partnerID=8YFLogxK

U2 - 10.1126/science.aax6752

DO - 10.1126/science.aax6752

M3 - Article

C2 - 31831638

AN - SCOPUS:85078742646

SN - 0036-8075

VL - 367

SP - 528

EP - 537

JO - Science

JF - Science

IS - 6477

ER -

Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Abstract

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