TY - JOUR AU - Cserép, Csaba AU - Pósfai, Balázs AU - Cserépné Szabadits, Eszter AU - Dénes, Ádám TI - Contactomics of Microglia and Intercellular Communication JF - ADVANCES IN NEUROBIOLOGY J2 - ADVANCES IN NEUROBIOLOGY VL - 37 PY - 2024 SP - 135 EP - 149 PG - 15 SN - 2190-5215 DO - 10.1007/978-3-031-55529-9_8 UR - https://m2.mtmt.hu/api/publication/35257522 ID - 35257522 LA - English DB - MTMT ER - TY - JOUR AU - Scheiblich, H. AU - Eikens, F. AU - Wischhof, L. AU - Opitz, S. AU - Jüngling, K. AU - Cserép, Csaba AU - Schmidt, S.V. AU - Lambertz, J. AU - Bellande, T. AU - Pósfai, Balázs AU - Geck, C. AU - Spitzer, J. AU - Odainic, A. AU - Castro-Gomez, S. AU - Schwartz, S. AU - Boussaad, I. AU - Krüger, R. AU - Glaab, E. AU - Di, Monte D.A. AU - Bano, D. AU - Dénes, Ádám AU - Latz, E. AU - Melki, R. AU - Pape, H.-C. AU - Heneka, M.T. TI - Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes JF - NEURON J2 - NEURON VL - 112 PY - 2024 IS - 18 SP - 3106 EP - 3125.e8 PG - 29 SN - 0896-6273 DO - 10.1016/j.neuron.2024.06.029 UR - https://m2.mtmt.hu/api/publication/35176925 ID - 35176925 LA - English DB - MTMT ER - TY - JOUR AU - Berki, Péter AU - Cserép, Csaba AU - Környei, Zsuzsanna AU - Pósfai, Balázs AU - Cserépné Szabadits, Eszter AU - Domonkos, Andor AU - Kellermayer, Anna AU - Nyerges, Miklós AU - Wei, Xiaofei AU - Mody, Istvan AU - Kunihiko, Araki AU - Beck, Heinz AU - Kaikai, He AU - Ya, Wang AU - Lénárt, Nikolett AU - Wu, Zhaofa AU - Jing, Miao AU - Li, Yulong AU - Gulyás, Attila AU - Dénes, Ádám TI - Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 15 PY - 2024 IS - 1 PG - 24 SN - 2041-1723 DO - 10.1038/s41467-024-49773-1 UR - https://m2.mtmt.hu/api/publication/35058848 ID - 35058848 LA - English DB - MTMT ER - TY - JOUR AU - Lénárt, Nikolett AU - Cserép, Csaba AU - Császár, Eszter AU - Pósfai, Balázs AU - Dénes, Ádám TI - Microglia–neuron–vascular interactions in ischemia JF - GLIA J2 - GLIA VL - 72 PY - 2024 IS - 5 SP - 833 EP - 856 PG - 24 SN - 0894-1491 DO - 10.1002/glia.24487 UR - https://m2.mtmt.hu/api/publication/34350929 ID - 34350929 AB - Cerebral ischemia is a devastating condition that results in impaired blood flow in the brain leading to acute brain injury. As the most common form of stroke, occlusion of cerebral arteries leads to a characteristic sequence of pathophysiological changes in the brain tissue. The mechanisms involved, and comorbidities that determine outcome after an ischemic event appear to be highly heterogeneous. On their own, the processes leading to neuronal injury in the absence of sufficient blood supply to meet the metabolic demand of the cells are complex and manifest at different temporal and spatial scales. While the contribution of non‐neuronal cells to stroke pathophysiology is increasingly recognized, recent data show that microglia, the main immune cells of the central nervous system parenchyma, play previously unrecognized roles in basic physiological processes beyond their inflammatory functions, which markedly change during ischemic conditions. In this review, we aim to discuss some of the known microglia–neuron–vascular interactions assumed to contribute to the acute and delayed pathologies after cerebral ischemia. Because the mechanisms of neuronal injury have been extensively discussed in several excellent previous reviews, here we focus on some recently explored pathways that may directly or indirectly shape neuronal injury through microglia‐related actions. These discoveries suggest that modulating gliovascular processes in different forms of stroke and other neurological disorders might have presently unexplored therapeutic potential in combination with neuroprotective and flow restoration strategies. LA - English DB - MTMT ER - TY - JOUR AU - Cserép, Csaba AU - Schwarcz, Dóra Anett AU - Pósfai, Balázs AU - László, Zsófia Ilona AU - Kellermayer, Anna AU - Környei, Zsuzsanna AU - Kisfali, Máté AU - Nyerges, Miklós AU - Lele, Zsolt AU - Katona, István AU - Dénes, Ádám TI - Microglial control of neuronal development via somatic purinergic junctions JF - CELL REPORTS J2 - CELL REP VL - 40 PY - 2022 IS - 12 PG - 22 SN - 2639-1856 DO - 10.1016/j.celrep.2022.111369 UR - https://m2.mtmt.hu/api/publication/33111942 ID - 33111942 N1 - “Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, 1083, Hungary “Momentum” Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, 1083, Hungary University of Dundee, School of Medicine, Dundee, DD1 9SY, United Kingdom Szentágothai János Doctoral School of Neurosciences, Semmelweis University, Budapest, 1083, Hungary Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, United States Cited By :19 Export Date: 27 August 2024 Correspondence Address: Cserép, C.; “Momentum” Laboratory of Neuroimmunology, Hungary; email: cserep.csaba@koki.hu Correspondence Address: Adam Denes; “Momentum” Laboratory of Neuroimmunology, Hungary; email: denes.adam@koki.hu Chemicals/CAS: lipocortin 5, 111237-10-6 Funding details: Magyar Tudományos Akadémia, MTA, LP2016-4/2016, LP2022-5/2022, ÚNKP-20-3-II, ÚNKP-20-5, ÚNKP-21-4, ÚNKP-21-5 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 129961 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding details: Richter Gedeon Talentum Alapítvány, 2017-1.2.1-NKP-2017-00002, 2020-1.2.4-TÉT-IPARI-2021-00005 Funding details: Richter Gedeon Talentum Alapítvány Funding details: Innovációs és Technológiai Minisztérium Funding text 1: We thank Drs. László Barna and Pál Vági for kindly providing microscopy support and Dóra Gali-Györkei, Balázs Pintér, and Erika Tischler for excellent technical assistance. The study was supported by “ Momentum ” research grants from the Hungarian Academy of Sciences ( LP2016-4/2016 and LP2022-5/2022 to Á.D.), ERC-CoG 724994 (to Á.D.), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (to C.C.), ÚNKP-20-3-II and ÚNKP-21-4 (to B.P.) and ÚNKP-20-5 and ÚNKP-21-5 (to C.C.), the New National Excellence Program of the Ministry for Innovation and Technology , the Gedeon Richter's Talentum Foundation (to A.D.S.), and by 2020-1.2.4-TÉT-IPARI-2021-00005 (to Á.D.). I.K. was supported by the National Brain Research Program ( 2017-1.2.1-NKP-2017-00002 ) and by the National Research, Development and Innovation Office , Hungary (Frontier Program 129961). The funding institutions had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Császár, Eszter AU - Lénárt, Nikolett AU - Cserép, Csaba AU - Környei, Zsuzsanna AU - Fekete, Rebeka AU - Pósfai, Balázs AU - Balázsfi, Diána AU - Hangya, Balázs AU - Schwarcz, Dóra Anett AU - Cserépné Szabadits, Eszter AU - Szöllősi, Dávid AU - Szigeti, Krisztián AU - Máthé, Domokos AU - West, Brian L AU - Tóthné Sviatkó, Katalin AU - Brás, Ana Rita AU - Mariani, Jean-Charles AU - Kliewer, Andrea AU - Lenkei, Zsolt AU - Hricisák, László AU - Benyó, Zoltán AU - Baranyi, Mária AU - Sperlágh, Beáta AU - Menyhárt, Ákos AU - Farkas, Eszter AU - Dénes, Ádám TI - Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. JF - JOURNAL OF EXPERIMENTAL MEDICINE J2 - J EXP MED VL - 219 PY - 2022 IS - 3 PG - 33 SN - 0022-1007 DO - 10.1084/jem.20211071 UR - https://m2.mtmt.hu/api/publication/32710992 ID - 32710992 AB - Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Krisztina AU - Lénárt, Nikolett AU - Berki, Péter AU - Fekete, Rebeka AU - Cserépné Szabadits, Eszter AU - Pósfai, Balázs AU - Cserép, Csaba AU - Alatshan, Ahmad AU - Benkő, Szilvia AU - Kiss, Dániel AU - Hübner, Christian A. AU - Gulyás, Attila AU - Kaila, Kai AU - Környei, Zsuzsanna AU - Dénes, Ádám TI - The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner JF - PLOS BIOLOGY J2 - PLOS BIOL VL - 20 PY - 2022 IS - 1 PG - 31 SN - 1544-9173 DO - 10.1371/journal.pbio.3001526 UR - https://m2.mtmt.hu/api/publication/32636201 ID - 32636201 N1 - Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Budapest, Hungary Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Doctoral School of Molecular Cellular and Immune Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Software Engineering Institute, John von Neumann Faculty of Informatics, Óbuda University, Budapest, Hungary University Hospital Jena, Friedrich Schiller University, Jena, Germany Molecular and Integrative Biosciences and Neuroscience Center (HiLIFE), University of Helsinki, Helsinki, Finland Export Date: 24 February 2022 CODEN: PBLIB Correspondence Address: Dénes, Á.; Momentum Laboratory of Neuroimmunology, Hungary; email: denes.adam@koki.hu Chemicals/CAS: bumetanide, 28395-03-1 Funding details: BO/00558/19/5, K131844, NKP-20 3-II, NKP-21-5, bolyai-janos-kutatasi-osztondij-105319 Funding details: Deutsche Forschungsgemeinschaft, DFG, SPP 1665 Funding details: Academy of Finland, AKA Funding details: Bundesministerium für Bildung und Forschung, BMBF Funding details: Magyar Tudományos Akadémia, MTA, 2019-2.1.7-ERA-NET-2020-00004, ERC-CoG 724994, LP2016-4/2016 Funding details: Sigrid Juséliuksen Säätiö Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Neuron Nadační Fond Na Podporu Vědy, Neuron, ACRoBAT 01EW1706 Funding details: Magyarország Kormánya Funding text 1: This work was supported by ?Momentum? research grant from the Hungarian Academy of Sciences (LP2016-4/2016 to A.D.; https://mta.hu/lendulet) and ERC-CoG 724994 (to A.D.; https://erc.europa.eu/), with contribution from 2019-2.1.7-ERA-NET-2020-00004 (https://nkfih. gov.hu). Additionally, this work was funded by Hungarian National Scientific Research Fund (NKFIH-OTKA Grant No. K131844 to S.B.), the J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences (to C.C. and N.L., BO/00558/19/5; https://mta.hu/bolyai-osztondij/ bolyai-janos-kutatasi-osztondij-105319), ?NKP-20 3-II (to B.P.) and ?NKP-21-5 (to C.C. and N.L.; http://www.unkp.gov.hu/unkp-rol) of the New National Excellence Program of the Ministry for Innovation and Technology, Hungary; German Research Foundation (SPP 1665; https://www.dfg. de/en/) and the Federal Ministry of Education and Research (NEURON ACRoBAT 01EW1706) to C.A. H.; and the Academy of Finland and Sigrid Jus?lius Foundation to K.K.. Prepared with the professional support of the Doctoral Scholarship Program of th Cooperative Doctoral Program of the Ministry of Innovation and Technology Financed from The National Research, Development and Innovation Fund (to B.P.). A.A. holds a Stipendium Hungaricum Scholarship from the Government of Hungary (https://stipendiumhungaricum.hu/). K. K.?s work was supported by the Academy of Finland and by the Sigrid Jus?lius Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank J?nos Szabadics for his valuable remarks on the electrophysiology part of the manuscript; L?szl? Barna and the Nikon Imaging Center at the Institute of Experimental Medicine for kindly providing microscopy support; D?ra Gali-Gy?rkei for her excellent technical assistance; and the Cell Biology Center at the Institute of Experimental Medicine. AB - The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1β (IL-1β), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Eszter Ágnes AU - Turiák, Lilla AU - Visnovitz, Tamás AU - Cserép, Csaba AU - Türk-Mázló, Anett AU - Sódar, Barbara AU - Försönits, András AU - Petővári, Gábor AU - Sebestyén, Anna AU - Komlósi, Zsolt AU - Drahos, László AU - Kittel, Ágnes AU - Nagy, György AU - Bácsi, Attila AU - Dénes, Ádám AU - Song Gho, Yong AU - Szabó-Taylor, Katalin AU - Buzás, Edit Irén TI - Formation of a protein corona on the surface of extracellular vesicles in blood plasma JF - JOURNAL OF EXTRACELLULAR VESICLES J2 - J EXTRACELLULAR VESICL VL - 10 PY - 2021 IS - 11 PG - 26 SN - 2001-3078 DO - 10.1002/jev2.12140 UR - https://m2.mtmt.hu/api/publication/32189675 ID - 32189675 N1 - Katalin É Szabó-Taylor and Edit I Buzás contributed equally. Funding information National Research, Development and Innovation Office NKFIH, Hungary, Grant/Award Numbers: OTKA11958, OTKA120237, OTKA125337, OTKA K131479, OTKA PD 121187, OTKA FK 131603, OTKA 131762, NVKP_16-1-2016-0017; Higher Education Institutional Excellence Program – Therapeutic development, Grant/Award Numbers:ÚNKP-19-3-I-SE-45, ÚNKP-20-5; New National Excellence Program of the Ministry for Innovation and Technology; Ministry for National Economy of Hungary, Grant/Award Numbers: VEKOP-2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00016, EFOP-3.6.3-VEKOP-16-2017-00009; Az orvos-,egészségtudományi- és gyógyszerészképzés tudományos muhelyeinek fejlesztése; European ̋Commission, Grant/Award Number: H2020-MSCA-ITN-2017-722148 TRAIN EV; Hungarian Academy of Sciences: János Bolyai Research Schol- arship and “Momentum”, Grant/Award Number: LP2016-4/2016; European Research Council, Grant/Award Numbers: ERC-CoG 724994, H2020-ITN-2018-813294-ENTRAIN; EU’s Horizon 2020 research and innovation program, Grant/Award Number: 739593 LA - English DB - MTMT ER - TY - JOUR AU - Cserép, Csaba AU - Pósfai, Balázs AU - Dénes, Ádám TI - Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions JF - NEURON J2 - NEURON VL - 109 PY - 2021 IS - 2 SP - 222 EP - 240 PG - 19 SN - 0896-6273 DO - 10.1016/j.neuron.2020.11.007 UR - https://m2.mtmt.hu/api/publication/31790751 ID - 31790751 N1 - Funding text 1: This work was supported by a “Momentum” research grant from the Hungarian Academy of Sciences ( LP2016-4/2016 to A.D.) and ERC-CoG 724994 (to A.D.), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (to C.C.), ÚNKP-20-3-II (to B.P.) and ÚNKP-20-5 (to C.C.) of the New National Excellence Program of the Ministry for Innovation and Technology, Hungary ; H2020-ITN-2018-813294-ENTRAIN (to A.D.); and SORLA-FIX 2019-2.1.7-ERANET-2020-00004 from the Ministry for Innovation and Technology, Hungary (to A.D.). AB - The functional contribution of microglia to normal brain development, healthy brain function, and neurological disorders is increasingly recognized. However, until recently, the nature of intercellular interactions mediating these effects remained largely unclear. Recent findings show microglia establishing direct contact with different compartments of neurons. Although communication between microglia and neurons involves intermediate cells and soluble factors, direct membrane contacts enable a more precisely regulated, dynamic, and highly effective form of interaction for fine-tuning neuronal responses and fate. Here, we summarize the known ultrastructural, molecular, and functional features of direct microglia-neuron interactions and their roles in brain disease. © 2020 Elsevier Inc. In this review, Cserép et al. summarize the compartment-specific ultrastructural, molecular, and functional features of direct microglia-neuron interactions and their role in disease. © 2020 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Cserép, Csaba AU - Pósfai, Balázs AU - Lénárt, Nikolett AU - Fekete, Rebeka AU - László, Zsófia Ilona AU - Lele, Zsolt AU - Orsolits, Barbara AU - Molnár, Gábor AU - Heindl, S AU - Schwarcz, Dóra Anett AU - Ujvári, Katinka AU - Környei, Zsuzsanna AU - Tóth, Krisztina AU - Cserépné 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 - Szipőcs, Róbert AU - Tamkun, MM AU - Gesierich, B AU - Duering, M AU - Katona, István AU - Liesz, A AU - Tamás, Gábor AU - Dénes, Ádám TI - Microglia monitor and protect neuronal function through specialized somatic purinergic junctions JF - SCIENCE J2 - SCIENCE VL - 367 PY - 2020 IS - 6477 SP - 528 EP - 537 PG - 11 SN - 0036-8075 DO - 10.1126/science.aax6752 UR - https://m2.mtmt.hu/api/publication/31294298 ID - 31294298 LA - English DB - MTMT ER -