dc.contributor.author | Baraibar Sierra, Andrés Mateo | |
dc.contributor.author | Colomer, Teresa | |
dc.contributor.author | Moreno García, Álvaro | |
dc.contributor.author | Bernal Chico, Ana | |
dc.contributor.author | Sánchez Martín, Ester | |
dc.contributor.author | Utrilla, Carmen | |
dc.contributor.author | Serrat, Roman | |
dc.contributor.author | Soria Gómez, Edgar | |
dc.contributor.author | Rodríguez-Antigüedad Zarranz, Alfredo | |
dc.contributor.author | Araque, Alfonso | |
dc.contributor.author | Matute Almau, Carlos José | |
dc.contributor.author | Marsicano, Giovanni | |
dc.contributor.author | Mato Santos, Susana | |
dc.date.accessioned | 2024-08-06T11:06:06Z | |
dc.date.available | 2024-08-06T11:06:06Z | |
dc.date.issued | 2024-10 | |
dc.identifier.citation | Brain, Behavior, and Immunity 121 : 192-210 (2024) | es_ES |
dc.identifier.issn | 1090-2139 | |
dc.identifier.uri | http://hdl.handle.net/10810/69175 | |
dc.description.abstract | Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber photometry in freely behaving mice, we found that acute EAE was associated with the emergence of spontaneously hyperactive cortical astrocytes exhibiting dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists. Abnormal astrocyte signaling by Gi and Gq protein coupled receptors was observed in the inflamed cortex. This was mirrored by treatments with pro-inflammatory factors both in vitro and ex vivo, suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, deregulated astrocyte calcium activity was associated with an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall, our data identify astrocyte-neuronal network dysfunctions as key pathological features of gray matter inflammation in multiple sclerosis and potentially additional neuroimmunological disorders. | es_ES |
dc.description.sponsorship | This work was funded by the Instituto de Salud Carlos III (PI21/00629, to S.M. and A.R.-A; CB06/05/00, to C.M.) and cofounded by the European Union, Basque Government (PIBA_2023_1_0046; 2023111031; IT1473-22, to S.M.; IT1203-19, to C.M.), ARSEP Foundation (ARSEP - 1310 to S.M. and G.M.), INSERM (to G.M.), the European Research Council (MiCaBra, ERC-2017-AdG-786467, to G.M.), Fondation pour la Recherche Medicale (FRM, DRM20101220445 to G.M.), Region Aquitaine (CanBrain, AAP2022A-2021-16763610 and -17219710 to G.M.); French State/Agence Nationale de la Recherche (HippObese, ANR-23-ce14-0004-03; ERA-Net Neuron CanShank, ANR-21-NEU2-0001-04, to G.M), La Caixa Research Health 2023 (PsychoCannabis, HR23-00793, to G.M.), Spanish Ministry of Science and Innovation (PID2019-109724RB-100 to C.M.; PGC2018-093990-A-I00, to E.S.-G.), National Institutes of Health-MH (MH, R01MH119355; NINDS, R01NS097312; NIDA, R01DA048822, to A.A.), Postdoctoral and Predoctoral Programs of the Basque Government (to A.M.B., T.C. A.M.-G., and C.U), Predoctoral Program of the UPV/EHU (to E.S.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/ERC/786467 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-109724RB-100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/PGC2018-093990-A-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.subject | astrocyte | es_ES |
dc.subject | calcium | es_ES |
dc.subject | gliotransmission | es_ES |
dc.subject | multiple sclerosis | es_ES |
dc.subject | cortex | es_ES |
dc.title | Autoimmune inflammation triggers aberrant astrocytic calcium signaling to impair synaptic plasticity | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license. | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0889159124004793 | es_ES |
dc.identifier.doi | 10.1016/j.bbi.2024.07.010 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |