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MicroCONtACT SIGNED

Microglial control of neuronal activity in the healthy and the injured brain

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MicroCONtACT" data sheet

The following table provides information about the project.

Coordinator
INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES 

Organization address
address: Szigony utca 43
city: Budapest
postcode: 1083
website: www.koki.hu

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Hungary [HU]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES HU (Budapest) coordinator 2˙000˙000.00

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 Project objective

Microglia are the main immune cells of the brain, but their role in brain injury is highly controversial due to the difficulties in selectively manipulating and imaging microglial actions in real time. Specifically, it is unclear whether microglia control neuronal survival after injury via shaping the activity of complex neuronal networks in vivo. To this end, we have combined fast in vivo two-photon imaging of neuronal calcium responses with selective microglial manipulation for the first time. Our data suggest that microglia constantly monitor and control neuronal network activity and these actions are essential to limit excitotoxicity and neuronal death after acute brain injury. We also identify microglia as key regulators of spreading depolarization in vivo. However, the underlying mechanisms remained unexplored. Here, I propose that microglia control neuronal excitability and based on preliminary data I set out to investigate how this occurs. We will combine selective, CSF1R-mediated microglia depletion with advanced neurophysiological methods such as in vivo calcium imaging and intracranial EEG for the first time, to reveal how microglia shape activity of complex neuronal networks in the healthy and the injured brain. Then, we will study microglia-neuron interactions from the network level to nanoscale level using in vivo two-photon imaging and super-resolution microscopy. We will apply novel chemogenic and optogenetic approaches to manipulate microglia in real time, assess their role in neuronal activity changes and investigate the molecular mechanisms in vitro and in vivo. Our unpublished data also suggest that inflammation – a key contributor to brain diseases – could disrupt microglia-neuron signaling and we set out to investigate the underlying mechanisms. By using state-of the-art research tools that had not been applied previously in this context, our studies are likely to reveal novel pathophysiological mechanisms relevant for common brain diseases.

 Publications

year authors and title journal last update
List of publications.
2020 Dániel P Varga, Ákos Menyhárt, Balázs Pósfai, Eszter Császár, Nikolett Lénárt, Csaba Cserép, Barbara Orsolits, Bernadett Martinecz, Tamás Szlepák, Ferenc Bari, Eszter Farkas, Ádám Dénes
Microglia alter the threshold of spreading depolarization and related potassium uptake in the mouse brain
published pages: 0271678X1990009, ISSN: 0271-678X, DOI: 10.1177/0271678x19900097
Journal of Cerebral Blood Flow & Metabolism 2020-04-07
2020 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 Szipőcs
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
published pages: 528-537, ISSN: 0036-8075, DOI: 10.1126/science.aax6752
Science 367/6477 2020-04-07
2019 Csaba Cserép, Balázs Pósfai, Barbara Orsolits, Gábor Molnár, Steffanie Heindl, Nikolett Lénárt, Rebeka Fekete, Zsófia I. László, Zsolt Lele, Anett D. Schwarcz, Katinka Ujvári, László Csiba, Tibor Hortobágyi, Zsófia Maglóczky, Bernadett Martinecz, Gábor Szabó, Ferenc Erdélyi, Róbert Szipőcs, Benno Gesierich, Marco Duering, István Katona, Arthur Liesz, Gábor Tamás, Ádám Dé
Microglia monitor and protect neuronal function via specialized somatic purinergic junctions
published pages: , ISSN: , DOI: 10.1101/606079
bioRxiv.org - the preprint server for Biology 2019-10-15
2019 Zsuzsanna Helyes, Valéria Tékus, Nikolett Szentes, Krisztina Pohóczky, Bálint Botz, Tamás Kiss, Ágnes Kemény, Zsuzsanna Környei, Krisztina Tóth, Nikolett Lénárt, Hajnalka Ábrahám, Emmanuel Pinteaux, Sheila Francis, Serena Sensi, Ádám Dénes, Andreas Goebel
Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms
published pages: 13067-13076, ISSN: 0027-8424, DOI: 10.1073/pnas.1820168116
Proceedings of the National Academy of Sciences 116/26 2019-10-07
2019 Lilla Lenart, Dora B. Balogh, Nikolett Lenart, Adrienn Barczi, Adam Hosszu, Tamas Farkas, Judit Hodrea, Attila J. Szabo, Krisztian Szigeti, Adam Denes, Andrea Fekete
Novel therapeutic potential of angiotensin receptor 1 blockade in a rat model of diabetes-associated depression parallels altered BDNF signalling
published pages: 1501-1513, ISSN: 0012-186X, DOI: 10.1007/s00125-019-4888-z
Diabetologia 62/8 2019-10-07
2019 Kelly L. Singel, Kassondra S. Grzankowski, A. N. M. Nazmul H. Khan, Melissa J. Grimm, Anthony C. D’Auria, Kayla Morrell, Kevin H. Eng, Bonnie Hylander, Paul C. Mayor, Tiffany R. Emmons, Nikolett Lénárt, Rebeka Fekete, Zsuzsanna Környei, Uma Muthukrishnan, Jonathan D. Gilthorpe, Constantin F. Urban, Kiyoshi Itagaki, Carl J. Hauser, Cynthia Leifer, Kirsten B. Moysich, Kunle Odunsi, Ádám Déne
Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer
published pages: 207-217, ISSN: 0007-0920, DOI: 10.1038/s41416-018-0339-8
British Journal of Cancer 120/2 2019-10-07
2018 Gergely Kovács, Zsuzsanna Környei, Krisztina Tóth, Mária Baranyi, János Brunner, Máté Neubrandt, Ádám Dénes, Beáta Sperlágh
Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia
published pages: 1-13, ISSN: 0143-4160, DOI: 10.1016/j.ceca.2018.07.010
Cell Calcium 75 2019-10-07
2018 Cserép, Csaba; Pósfai, Balázs; Schwarcz, Anett Dóra; Dénes, Ádám
Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites
published pages: , ISSN: 2373-2822, DOI: 10.1101/216093
eNeuro 1 2019-04-18
2018 Rebeka Fekete, Csaba Cserép, Nikolett Lénárt, Krisztina Tóth, Barbara Orsolits, Bernadett Martinecz, Előd Méhes, Bálint Szabó, Valéria Németh, Balázs Gönci, Beáta Sperlágh, Zsolt Boldogkői, Ágnes Kittel, Mária Baranyi, Szilamér Ferenczi, Krisztina Kovács, Gergely Szalay, Balázs Rózsa, Connor Webb, Gabor G. Kovacs, Tibor Hortobágyi, Brian L. West, Zsuzsanna Környei, Ádám Dénes
Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms
published pages: 461-482, ISSN: 0001-6322, DOI: 10.1007/s00401-018-1885-0
Acta Neuropathologica 136/3 2019-04-18
2018 Virág T. Takács, Csaba Cserép, Dániel Schlingloff, Balázs Pósfai, András Szőnyi, Katalin E. Sos, Zsuzsanna Környei, Ádám Dénes, Attila I. Gulyás, Tamás F. Freund, Gábor Nyiri
Co-transmission of acetylcholine and GABA regulates hippocampal states
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05136-1
Nature Communications 9/1 2019-04-18
2018 Balázs Pósfai, Csaba Cserép, Barbara Orsolits, Ádám Dénes
New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective
published pages: , ISSN: 0306-4522, DOI: 10.1016/j.neuroscience.2018.04.046
Neuroscience 2019-04-18

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