{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:37:13Z","timestamp":1790779033102,"version":"4.1.0"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","award":["2022\/R-Multi\/026"],"award-info":[{"award-number":["2022\/R-Multi\/026"]}],"id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["Linea D1"],"award-info":[{"award-number":["Linea D1"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["Linea D1"],"award-info":[{"award-number":["Linea D1"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discov."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cognitive impairment (CI) is a hallmark of multiple sclerosis (MS). Despite its relevance, however, knowledge of the key steps involved in its pathogenesis remains incomplete. Consequently, predictive biomarkers and actionable therapeutic options to counteract CI in MS patients are not available. To identify changes associated with CI in MS, we performed transcriptomic analyses of the prefrontal cortex (PFC), a cortical region relevant for cognition, in the experimental autoimmune encephalomyelitis (EAE) mouse model. Our analyses highlighted the strong upregulation of inflammatory pathways in the PFC of EAE mice. Clustering of the top differentially expressed genes (DEGs) in the PFC identified a low (EAE-L) and a high (EAE-H) inflammation subgroup. Notably, enhanced inflammation in the EAE PFC caused increased changes in expression levels of MS-associated genes with relevance for CI. Cell Type-Specific Expression Analysis (CSEA) and morphological analyses indicated that, while EAE-L mice showed only microglia activation, EAEH mice also displayed the involvement of astrocytes, consistent with a more advanced stage of disease. Moreover, neuronal genes were only downregulated in the EAE-H PFC. Analysis of cognitive performance in pre-symptomatic EAE mice revealed that high expression of genes associated with the antigen presentation and the complement pathways was associated with CI. Moreover, expression of C1q complement proteins was increased in the cerebrospinal fluid of MS patients affected by CI. These findings indicate that inflammation in the PFC during EAE is associated with CI and identify a subset of inflammatory genes that may represent early markers and risk factors for functional PFC impairment and loss of cognitive performance in MS patients.<\/jats:p>","DOI":"10.1038\/s41420-026-03051-9","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:16:59Z","timestamp":1774451819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptome analysis of the prefrontal cortex identifies inflammatory genes associated with cognitive impairment in a model of multiple sclerosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Luca","family":"Zupo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Adinolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-535X","authenticated-orcid":false,"given":"Marco","family":"Pieraccioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Corvino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ceci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-7311","authenticated-orcid":false,"given":"Valerio","family":"Chiurchi\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sperandei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Di Filippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Di Sante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Geloso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-8266","authenticated-orcid":false,"given":"Claudio","family":"Sette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"3051_CR1","doi-asserted-by":"publisher","unstructured":"Schiavolin S, Leonardi M, Giovannetti AM, Antozzi C, Brambilla L, Confalonieri P, et al. Factors related to difficulties with employment in patients with multiple sclerosis: a review of 2002-2011 literature. International Journal of Rehabilitation Research. 2013. https:\/\/doi.org\/10.1097\/MRR.0b013e32835c79ea","DOI":"10.1097\/MRR.0b013e32835c79ea"},{"key":"3051_CR2","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/S1474-4422(08)70259-X","volume":"7","author":"ND Chiaravalloti","year":"2008","unstructured":"Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7:1139\u201351. https:\/\/doi.org\/10.1016\/S1474-4422(08)70259-X.","journal-title":"Lancet Neurol"},{"key":"3051_CR3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41582-020-03551","volume":"16","author":"J DeLuca","year":"2020","unstructured":"DeLuca J, Chiaravalloti ND, Sandroff BM. Treatment and management of cognitive dysfunction in patients with multiple sclerosis. Nat Rev Neurol. 2020;16:319\u201332. https:\/\/doi.org\/10.1038\/s41582-020-03551.","journal-title":"Nat Rev Neurol"},{"key":"3051_CR4","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","volume":"19","author":"RHB Benedict","year":"2020","unstructured":"Benedict RHB, Amato MP, DeLuca J, Geurts JJG. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol. 2020;19:860\u201371. https:\/\/doi.org\/10.1016\/S1474-4422(20)30277-5.","journal-title":"Lancet Neurol"},{"key":"3051_CR5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nrn3900","volume":"16","author":"M Calabrese","year":"2015","unstructured":"Calabrese M, Magliozzi R, Ciccarelli O, Geurts JJG, Reynolds R, Martin R. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci. 2015;16:147\u201358. https:\/\/doi.org\/10.1038\/nrn3900.","journal-title":"Nat Rev Neurosci"},{"key":"3051_CR6","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1177\/13524585221116273","volume":"29","author":"E Portaccio","year":"2023","unstructured":"Portaccio E, Amato MP. Reliable change indices for cognitive assessment of patients with multiple sclerosis. Mult Scler J. 2023;29:485\u20136. https:\/\/doi.org\/10.1177\/13524585221116273.","journal-title":"Mult Scler J"},{"key":"3051_CR7","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41583-018-00539","volume":"19","author":"M Di Filippo","year":"2018","unstructured":"Di Filippo M, Portaccio E, Mancini A, Calabresi P. Multiple sclerosis and cognition: synaptic failure and network dysfunction. Nat Rev Neurosci. 2018;19:599\u2013609. https:\/\/doi.org\/10.1038\/s41583-018-00539.","journal-title":"Nat Rev Neurosci"},{"key":"3051_CR8","doi-asserted-by":"publisher","first-page":"12312","DOI":"10.1523\/JNEUROSCI.2796-12.2012","volume":"32","author":"MO Ziehn","year":"2012","unstructured":"Ziehn MO, Avedisian AA, Dervin SM, Umeda EA, O'Dell TJ, Voskuhl RR. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012;32:12312\u201324. https:\/\/doi.org\/10.1523\/JNEUROSCI.2796-12.2012.","journal-title":"J Neurosci"},{"key":"3051_CR9","doi-asserted-by":"publisher","first-page":"113497","DOI":"10.1016\/j.expneurol.2020.113497","volume":"335","author":"E Marchese","year":"2021","unstructured":"Marchese E, Valentini M, Di Sante G, Cesari E, Adinolfi A, Corvino V, et al. Alternative splicing of neurexins 1\u20133 is modulated by neuroinflammation in the prefrontal cortex of a murine model of multiple sclerosis. Exp Neurol. 2021;335:113497 https:\/\/doi.org\/10.1016\/j.expneurol.2020.113497.","journal-title":"Exp Neurol"},{"key":"3051_CR10","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41586-019-1404-z","volume":"573","author":"L Schirmer","year":"2019","unstructured":"Schirmer L, Velmeshev D, Holmqvist S, Kaufmann M, Werneburg S, Jung D, et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature. 2019;573:75\u201382. https:\/\/doi.org\/10.1038\/s41586-019-1404-z.","journal-title":"Nature"},{"key":"3051_CR11","doi-asserted-by":"publisher","unstructured":"Kihara Y, Zhu Y, Jonnalagadda D, Romanow W, Palmer C, Siddoway B, et al. Single-nucleus RNA-seq of normal-appearing brain regions in relapsing-remitting vs. secondary progressive multiple sclerosis: implications for the efficacy of fingolimod. Front Cell Neurosci. 2022;16. https:\/\/doi.org\/10.3389\/fncel.2022.918041.","DOI":"10.3389\/fncel.2022.918041"},{"key":"3051_CR12","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s11682-012-9170-7","volume":"8","author":"U Nocentini","year":"2014","unstructured":"Nocentini U, Bozzali M, Span\u00f2 B, Cercignani M, Serra L, Basile B, et al. Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. Brain Imaging Behav. 2014;8:378\u201386. https:\/\/doi.org\/10.1007\/s11682-012-9170-7.","journal-title":"Brain Imaging Behav"},{"key":"3051_CR13","doi-asserted-by":"publisher","unstructured":"Du XF, Liu J, Hua QF, Wu YJ. Relapsing-remitting multiple sclerosis is associated with regional brain activity deficits in motor- and cognitive-related brain areas. Front Neurol. 2019;10. https:\/\/doi.org\/10.3389\/fneur.2019.01136.","DOI":"10.3389\/fneur.2019.01136"},{"key":"3051_CR14","doi-asserted-by":"publisher","unstructured":"Cortese R, Battaglini M, Stromillo ML, Luchetti L, Leoncini M, Gentile G, et al. Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis. J Neurol. 2024;271:4897\u2013908. https:\/\/doi.org\/10.1007\/s00415-024-12290-8.","DOI":"10.1007\/s00415-024-12290-8"},{"key":"3051_CR15","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.acn.2007.04.003","volume":"22","author":"O Santiago","year":"2007","unstructured":"Santiago O, Guardia J, Casado V, Carmona O, Arbizu T. Specificity of frontal dysfunctions in relapsing-remitting multiple sclerosis. Arch Clin Neuropsychol. 2007;22:623\u20139. https:\/\/doi.org\/10.1016\/j.acn.2007.04.003.","journal-title":"Arch Clin Neuropsychol"},{"key":"3051_CR16","doi-asserted-by":"publisher","unstructured":"Curti E, Graziuso S, Tsantes E, Crisi G, Granella F. Correlation between cortical lesions and cognitive impairment in multiple sclerosis. Brain Behav. 2018;8. https:\/\/doi.org\/10.1002\/brb3.955","DOI":"10.1002\/brb3.955"},{"key":"3051_CR17","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1176\/jnp.14.1.44","volume":"14","author":"RHB Benedict","year":"2002","unstructured":"Benedict RHB, Bakshi R, Simon JH, Priore R, Miller C, Munschauer F. Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis. J Neuropsychiatry Clin Neurosci. 2002;14:44\u201351. https:\/\/doi.org\/10.1176\/jnp.14.1.44.","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"3051_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40713-4","volume":"9","author":"R Aharoni","year":"2019","unstructured":"Aharoni R, Schottlender N, Bar-Lev DD, Eilam R, Sela M, Tsoory M, et al. Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate. Sci Rep. 2019;9:4140. https:\/\/doi.org\/10.1038\/s41598-019-40713-4.","journal-title":"Sci Rep"},{"key":"3051_CR19","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1038\/s41593-018-0193-2","volume":"21","author":"E Ellwardt","year":"2018","unstructured":"Ellwardt E, Pramanik G, Luchtman D, Novkovic T, Jubal ER, Vogt J, et al. Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis. Nat Neurosci. 2018;21:1392\u2013403. https:\/\/doi.org\/10.1038\/s41593-018-0193-2.","journal-title":"Nat Neurosci"},{"key":"3051_CR20","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s11481-023-10080-z","volume":"18","author":"DS Peres","year":"2023","unstructured":"Peres DS, Viero FT, Rodrigues P, de Barros Bernardes L, da Silva NAR, Lima IR, et al. Characterization of depression- and anxiety-like behaviours in a mouse model of relapsing-remitting multiple sclerosis. J Neuroimmune Pharmacol. 2023;18:235\u201347. https:\/\/doi.org\/10.1007\/s11481-023-10080-z.","journal-title":"J Neuroimmune Pharmacol"},{"key":"3051_CR21","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1093\/brain\/awm219","volume":"130","author":"S Rasmussen","year":"2007","unstructured":"Rasmussen S, Wang Y, Kivis\u00e4kk P, Bronson RT, Meyer M, Imitola J, et al. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing-remitting experimental autoimmune encephalomyelitis. Brain. 2007;130:2816\u201329. https:\/\/doi.org\/10.1093\/brain\/awm219.","journal-title":"Brain"},{"key":"3051_CR22","doi-asserted-by":"publisher","unstructured":"Piermattei A, Migliara G, Di Sante G, Foti M, Hayrabedyan SB, Papagna A, et al. Toll-like receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium Tuberculosis and modulates autoimmune encephalomyelitis. Front Immunol. 2016;7. https:\/\/doi.org\/10.3389\/fimmu.2016.00191","DOI":"10.3389\/fimmu.2016.00191"},{"key":"3051_CR23","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","volume":"9","author":"HS Kwon","year":"2020","unstructured":"Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020;9:42 https:\/\/doi.org\/10.1186\/s40035-020-00221-2.","journal-title":"Transl Neurodegener"},{"key":"3051_CR24","doi-asserted-by":"publisher","unstructured":"Serre-Miranda C, Roque S, Santos NC, Costa P, Sousa N, Palha JA, et al. Cognition is associated with peripheral immune molecules in healthy older adults: a cross-sectional study. Front Immunol. 2020;11. https:\/\/doi.org\/10.3389\/fimmu.2020.02045.","DOI":"10.3389\/fimmu.2020.02045"},{"key":"3051_CR25","doi-asserted-by":"publisher","first-page":"110094","DOI":"10.1016\/j.celrep.2021.110094","volume":"37","author":"M Di Filippo","year":"2021","unstructured":"Di Filippo M, Mancini A, Bellingacci L, Gaetani L, Mazzocchetti P, Zelante T, et al. Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis. Cell Rep. 2021;37:110094 https:\/\/doi.org\/10.1016\/j.celrep.2021.110094.","journal-title":"Cell Rep"},{"key":"3051_CR26","doi-asserted-by":"publisher","first-page":"109508","DOI":"10.1016\/j.celrep.2021.109508","volume":"36","author":"B Diaz-Castro","year":"2021","unstructured":"Diaz-Castro B, Bernstein AM, Coppola G, Sofroniew MV, Khakh BS. Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation. Cell Rep. 2021;36:109508 https:\/\/doi.org\/10.1016\/j.celrep.2021.109508.","journal-title":"Cell Rep"},{"key":"3051_CR27","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3390\/cells10030686","volume":"10","author":"MC Geloso","year":"2021","unstructured":"Geloso MC, D\u2019ambrosi N. Microglial pruning: relevance for synaptic dysfunction in multiple sclerosis and related experimental models. Cells. 2021;10:686 https:\/\/doi.org\/10.3390\/cells10030686.","journal-title":"Cells"},{"key":"3051_CR28","doi-asserted-by":"publisher","unstructured":"Guzman-Martinez L, Maccioni RB, Andrade V, Navarrete LP, Pastor MG, Ramos-Escobar N Neuroinflammation as a common feature of neurodegenerative disorders. Front Pharmacol. 2019, 10. https:\/\/doi.org\/10.3389\/fphar.2019.01008","DOI":"10.3389\/fphar.2019.01008"},{"key":"3051_CR29","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.cell.2023.03.008","volume":"186","author":"M Charabati","year":"2023","unstructured":"Charabati M, Wheeler MA, Weiner HL, Quintana FJ. Multiple sclerosis: neuroimmune crosstalk and therapeutic targeting. Cell. 2023;186:1309\u201327. https:\/\/doi.org\/10.1016\/j.cell.2023.03.008.","journal-title":"Cell"},{"key":"3051_CR30","doi-asserted-by":"publisher","unstructured":"Negro-Demontel L, Maleki AF, Reich DS, Kemper C. The complement system in neurodegenerative and inflammatory diseases of the central nervous system. Front Neurol. 2024;15. https:\/\/doi.org\/10.3389\/fneur.2024.1396520","DOI":"10.3389\/fneur.2024.1396520"},{"key":"3051_CR31","doi-asserted-by":"publisher","unstructured":"Pi\u00f1ero J, Ram\u00edrez-Anguita JM, Sa\u00fcch-Pitarch J, Ronzano F, Centeno E, Sanz F, et al. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 2020;48. https:\/\/doi.org\/10.1093\/nar\/gkz1021","DOI":"10.1093\/nar\/gkz1021"},{"key":"3051_CR32","doi-asserted-by":"publisher","first-page":"5003","DOI":"10.1016\/j.cell.2025.06.030","volume":"188","author":"T Krolak","year":"2025","unstructured":"Krolak T, Kaplan L, Navas K, Chen L, Birmingham A, Ryvkin D, et al. Brain endothelial gap junction coupling enables rapid vasodilation propagation during neurovascular coupling. Cell. 2025;188:5003\u20135019.e22. https:\/\/doi.org\/10.1016\/j.cell.2025.06.030.","journal-title":"Cell"},{"key":"3051_CR33","doi-asserted-by":"publisher","unstructured":"Benedek G, Meza-Romero R, Jordan K, Zhang Y, Nguyen H, Kent G, et al. MIF and D-DT are potential disease severity modifiers in male MS subjects. Proc Natl Acad Sci USA. 2017;114. https:\/\/doi.org\/10.1073\/pnas.1712288114","DOI":"10.1073\/pnas.1712288114"},{"key":"3051_CR34","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41590-020-0661-1","volume":"21","author":"A Giladi","year":"2020","unstructured":"Giladi A, Wagner LK, Li H, D\u00f6rr D, Medaglia C, Paul F, et al. Cxcl10 + monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation. Nat Immunol. 2020;21:525\u201334. https:\/\/doi.org\/10.1038\/s41590-020-0661-1.","journal-title":"Nat Immunol"},{"key":"3051_CR35","doi-asserted-by":"publisher","first-page":"619","DOI":"10.2147\/JIR.S270872","volume":"13","author":"S Dhaiban","year":"2020","unstructured":"Dhaiban S, Al-Ani M, Elemam NM, Maghazachi AA. Targeting chemokines and chemokine receptors in multiple sclerosis and experimental autoimmune encephalomyelitis. J Inflamm Res. 2020;13:619\u201333. https:\/\/doi.org\/10.2147\/JIR.S270872.","journal-title":"J Inflamm Res"},{"key":"3051_CR36","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.coi.2016.03.004","volume":"40","author":"LJ Stern","year":"2016","unstructured":"Stern LJ, Santambrogio L. The melting pot of the MHC II peptidome. Curr Opin Immunol. 2016;40:70\u201377. https:\/\/doi.org\/10.1016\/j.coi.2016.03.004.","journal-title":"Curr Opin Immunol"},{"key":"3051_CR37","doi-asserted-by":"publisher","first-page":"D870","DOI":"10.1093\/nar\/gkac947","volume":"51","author":"C Hu","year":"2023","unstructured":"Hu C, Li T, Xu Y, Zhang X, Li F, Bai J, et al. CellMarker 2.0: an updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data. Nucleic Acids Res. 2023;51:D870\u2013D876. https:\/\/doi.org\/10.1093\/nar\/gkac947.","journal-title":"Nucleic Acids Res"},{"key":"3051_CR38","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1212\/01.wnl.0000223832.66286.e4","volume":"67","author":"M Bugiani","year":"2006","unstructured":"Bugiani M, Al Shahwan S, Lamantea E, Bizzi A, Bakhsh E, Moroni I, et al. GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy. Neurology. 2006;67:273\u20139. https:\/\/doi.org\/10.1212\/01.wnl.0000223832.66286.e4.","journal-title":"Neurology"},{"key":"3051_CR39","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1385\/NMM:8:1-2:107","volume":"8","author":"KA Kleopa","year":"2006","unstructured":"Kleopa KA, Scherer SS. Molecular genetics of X-linked Charcot-Marie-Tooth disease. Neuromol Med. 2006;8:107\u201322. https:\/\/doi.org\/10.1385\/NMM:8:1-2:107.","journal-title":"Neuromol Med"},{"key":"3051_CR40","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1523\/JNEUROSCI.4488-13.2014","volume":"34","author":"X Xu","year":"2014","unstructured":"Xu X, Wells AB, O'Brien DR, Nehorai A, Dougherty JD. Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders. J Neurosci. 2014;34:1420\u201331. https:\/\/doi.org\/10.1523\/JNEUROSCI.4488-13.2014.","journal-title":"J Neurosci"},{"key":"3051_CR41","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/glia.22616","volume":"62","author":"R Brambilla","year":"2014","unstructured":"Brambilla R, Morton PD, Ashbaugh JJ, Karmally S, Lambertsen KL, Bethea JR. Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination. Glia. 2014;62:452\u201367. https:\/\/doi.org\/10.1002\/glia.22616.","journal-title":"Glia"},{"key":"3051_CR42","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jneuroim.2016.09.010","volume":"299","author":"R Waller","year":"2016","unstructured":"Waller R, Woodroofe MN, Wharton SB, Ince PG, Francese S, Heath PR, et al. Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role. J Neuroimmunol. 2016;299:139\u201346. https:\/\/doi.org\/10.1016\/j.jneuroim.2016.09.010.","journal-title":"J Neuroimmunol"},{"key":"3051_CR43","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jocn.2009.05.006","volume":"17","author":"I Yang","year":"2010","unstructured":"Yang I, Han SJ, Kaur G, Crane C, Parsa AT. The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci. 2010;17:6\u201310. https:\/\/doi.org\/10.1016\/j.jocn.2009.05.006.","journal-title":"J Clin Neurosci"},{"key":"3051_CR44","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/mp.2014.162","volume":"20","author":"J Rossier","year":"2015","unstructured":"Rossier J, Bernard A, Cabungcal JH, Perrenoud Q, Savoye A, Gallopin T, et al. Cortical fastspiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin. Mol Psychiatry. 2015;20:154\u201361. https:\/\/doi.org\/10.1038\/mp.2014.162.","journal-title":"Mol Psychiatry"},{"key":"3051_CR45","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.biopsych.2017.05.024","volume":"82","author":"C Fee","year":"2017","unstructured":"Fee C, Banasr M, Sibille E. Somatostatin-positive gamma-aminobutyric acid interneuron deficits in depression: cortical microcircuit and therapeutic perspectives. Biol Psychiatry. 2017;82:549\u201359. https:\/\/doi.org\/10.1016\/j.biopsych.2017.05.024.","journal-title":"Biol Psychiatry"},{"key":"3051_CR46","doi-asserted-by":"publisher","unstructured":"Tutukova S, Tarabykin V, Hernandez-Miranda LR. The role of neurod genes in brain development, function, and disease. Front Mol Neurosci. 2021;14. https:\/\/doi.org\/10.3389\/fnmol.2021.662774","DOI":"10.3389\/fnmol.2021.662774"},{"key":"3051_CR47","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1523\/JNEUROSCI.2768-16.2016","volume":"37","author":"SJ Lee","year":"2017","unstructured":"Lee SJ, Wei M, Zhang C, Maxeiner S, Pak C, Calado Botelho S, et al. Presynaptic neuronal pentraxin receptor organizes excitatory and inhibitory synapses. J Neurosci. 2017;37:1062\u201380. https:\/\/doi.org\/10.1523\/JNEUROSCI.2768-16.2016.","journal-title":"J Neurosci"},{"key":"3051_CR48","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1126\/science.aai8355","volume":"355","author":"GH Diering","year":"2017","unstructured":"Diering GH, Nirujogi RS, Roth RH, Worley PF, Pandey A, Huganir RL. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science. 2017;355:511\u20135. https:\/\/doi.org\/10.1126\/science.aai8355.","journal-title":"Science"},{"key":"3051_CR49","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.4103\/1673-5374.371350","volume":"18","author":"PS Potru","year":"2023","unstructured":"Potru PS, Spittau B. CD74: a prospective marker for reactive microglia? Neural Regen Res. 2023;18:2673\u20134. https:\/\/doi.org\/10.4103\/1673-5374.371350.","journal-title":"Neural Regen Res"},{"key":"3051_CR50","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41586021-03892-7","volume":"597","author":"M Absinta","year":"2021","unstructured":"Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J, et al. A lymphocyte\u2013microglia\u2013 astrocyte axis in chronic active multiple sclerosis. Nature. 2021;597:709\u201314. https:\/\/doi.org\/10.1038\/s41586021-03892-7.","journal-title":"Nature"},{"key":"3051_CR51","doi-asserted-by":"publisher","unstructured":"Drake SS, Zaman A, Simas T, Fournier AE. Comparing RNA-sequencing datasets from astrocytes, oligodendrocytes, and microglia in multiple sclerosis identifies novel dysregulated genes relevant to inflammation and myelination. WIREs Mech Dis. 2023;15. https:\/\/doi.org\/10.1002\/wsbm.1594","DOI":"10.1002\/wsbm.1594"},{"key":"3051_CR52","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1093\/cercor\/bht245","volume":"25","author":"GRI Barker","year":"2015","unstructured":"Barker GRI, Warburton EC. Object-in-place associative recognition memory depends on glutamate receptor neurotransmission within two defined hippocampal-cortical circuits: a critical role for AMPA and NMDA receptors in the hippocampus, perirhinal, and prefrontal cortices. Cereb Cortex. 2015;25:472\u201381. https:\/\/doi.org\/10.1093\/cercor\/bht245.","journal-title":"Cereb Cortex"},{"key":"3051_CR53","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.neuron.2004.05.013","volume":"42","author":"JZ Xiang","year":"2004","unstructured":"Xiang JZ, Brown MW. Neuronal responses related to long-term recognition memory processes in prefrontal cortex. Neuron. 2004;42:817\u201329. https:\/\/doi.org\/10.1016\/j.neuron.2004.05.013.","journal-title":"Neuron"},{"key":"3051_CR54","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.immuni.2019.12.004","volume":"52","author":"S Werneburg","year":"2020","unstructured":"Werneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM, et al. Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity. 2020;52:167\u2013182.e7. https:\/\/doi.org\/10.1016\/j.immuni.2019.12.004.","journal-title":"Immunity"},{"key":"3051_CR55","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41386-021-01132-0","volume":"47","author":"NP Friedman","year":"2022","unstructured":"Friedman NP, Robbins TW. The role of prefrontal cortex in cognitive control and executive function. Neuropsychopharmacology. 2022;47:72\u201389. https:\/\/doi.org\/10.1038\/s41386-021-01132-0.","journal-title":"Neuropsychopharmacology"},{"key":"3051_CR56","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/S1053-8119(03)00117-4","volume":"19","author":"A Charil","year":"2003","unstructured":"Charil A, Zijdenbos AP, Taylor J, Boelman C, Worsley KJ, Evans AC, et al. Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets. Neuroimage. 2003;19:532\u201344. https:\/\/doi.org\/10.1016\/S1053-8119(03)00117-4.","journal-title":"Neuroimage"},{"key":"3051_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4061\/2011\/932351","volume":"2011","author":"G Disanto","year":"2011","unstructured":"Disanto G, Berlanga AJ, Handel AE, Para AE, Burrell AM, Fries A, et al. Heterogeneity in multiple sclerosis: Scratching the surface of a complex disease. Autoimmune Dis. 2011;2011:1\u201312. https:\/\/doi.org\/10.4061\/2011\/932351.","journal-title":"Autoimmune Dis"},{"key":"3051_CR58","doi-asserted-by":"publisher","first-page":"e1005757","DOI":"10.1371\/journal.pcbi.1005757","volume":"13","author":"E Kotelnikova","year":"2017","unstructured":"Kotelnikova E, Kiani NA, Abad E, Martinez-Lapiscina EH, Andorra M, Zubizarreta I, et al. Dynamics and heterogeneity of brain damage in multiple sclerosis. PLoS Comput Biol. 2017;13:e1005757 https:\/\/doi.org\/10.1371\/journal.pcbi.1005757.","journal-title":"PLoS Comput Biol"},{"key":"3051_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44658-1","volume":"15","author":"HE Salapa","year":"2024","unstructured":"Salapa HE, Thibault PA, Libner CD, Ding Y, Clarke JPWE, Denomy C, et al. hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS). Nat Commun. 2024;15:356. https:\/\/doi.org\/10.1038\/s41467-023-44658-1.","journal-title":"Nat Commun"},{"key":"3051_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12565-021-00631-w","volume":"97","author":"Y Hattori","year":"2022","unstructured":"Hattori Y. The behavior and functions of embryonic microglia. Anat Sci Int. 2022;97:1\u201314. https:\/\/doi.org\/10.1007\/s12565-021-00631-w.","journal-title":"Anat Sci Int"},{"key":"3051_CR61","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.nbd.2011.03.003","volume":"42","author":"SK Wasseff","year":"2011","unstructured":"Wasseff SK, Scherer SS. Cx32 and Cx47 mediate oligodendrocyte:astrocyte and oligodendrocyte:oligodendrocyte gap junction coupling. Neurobiol Dis. 2011;42:506\u201313. https:\/\/doi.org\/10.1016\/j.nbd.2011.03.003.","journal-title":"Neurobiol Dis"},{"key":"3051_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0080-8","volume":"8","author":"MS Khan","year":"2018","unstructured":"Khan MS, Boileau I, Kolla N, Mizrahi R. A systematic review of the role of the nociceptin receptor system in stress, cognition, and reward: Relevance to schizophrenia. Transl Psychiatry. 2018;8:38. https:\/\/doi.org\/10.1038\/s41398-017-0080-8.","journal-title":"Transl Psychiatry"},{"key":"3051_CR63","doi-asserted-by":"publisher","first-page":"34","DOI":"10.2174\/13895575130104","volume":"13","author":"G Tuboly","year":"2012","unstructured":"Tuboly G, Vecsei L. Somatostatin and cognitive function in neurodegenerative disorders. MiniRev Med Chem. 2012;13:34\u201346. https:\/\/doi.org\/10.2174\/13895575130104.","journal-title":"MiniRev Med Chem"},{"key":"3051_CR64","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.biopsych.2004.10.034","volume":"57","author":"L Erraji-Benchekroun","year":"2005","unstructured":"Erraji-Benchekroun L, Underwood MD, Arango V, Galfalvy H, Pavlidis P, Smyrniotopoulos P, et al. Molecular aging in human prefrontal cortex is selective and continuous throughout adult life. Biol Psychiatry. 2005;57:549\u201358. https:\/\/doi.org\/10.1016\/j.biopsych.2004.10.034.","journal-title":"Biol Psychiatry"},{"key":"3051_CR65","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.bcp.2013.06.001","volume":"86","author":"J Basivireddy","year":"2013","unstructured":"Basivireddy J, Somvanshi RK, Romero IA, Weksler BB, Couraud PO, Oger J, et al. Somatostatin preserved blood brain barrier against cytokine induced alterations: possible role in multiple sclerosis. Biochem Pharm. 2013;86:497\u2013507. https:\/\/doi.org\/10.1016\/j.bcp.2013.06.001.","journal-title":"Biochem Pharm"},{"key":"3051_CR66","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1136\/jnnp-2019-322493","volume":"91","author":"EL Van Der Ende","year":"2020","unstructured":"Van Der Ende EL, Xiao M, Xu D, Poos JM, Panman JL, Jiskoot LC, et al. Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2020;91:612\u201321. https:\/\/doi.org\/10.1136\/jnnp-2019-322493.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"3051_CR67","doi-asserted-by":"publisher","unstructured":"Matejuk A, Ransohoff RM. Crosstalk between astrocytes and microglia: an overview. Front Immunol. 2020;11. https:\/\/doi.org\/10.3389\/fimmu.2020.01416","DOI":"10.3389\/fimmu.2020.01416"},{"key":"3051_CR68","doi-asserted-by":"publisher","unstructured":"Jord\u00e3o, MJC R, Sankowski SM, Brendecke G, Sagar, Locatelli G, Tai YH, et al. Neuroimmunology: single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science. 2019;363. https:\/\/doi.org\/10.1126\/science.aat7554","DOI":"10.1126\/science.aat7554"},{"key":"3051_CR69","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1016\/S0140-6736(03)13088-7","volume":"361","author":"H Lassmann","year":"2003","unstructured":"Lassmann H. Brain damage when multiple sclerosis is diagnosed clinically. Lancet. 2003;361:1317\u20138. https:\/\/doi.org\/10.1016\/S0140-6736(03)13088-7.","journal-title":"Lancet"},{"key":"3051_CR70","doi-asserted-by":"publisher","unstructured":"Jakimovski D, Bittner S, Zivadinov R, Morrow SA, Benedict RH, Zipp F, et al. Multiple sclerosis. Lancet. 2024;403:183\u2013202. https:\/\/doi.org\/10.1016\/S01406736(23)01473-3","DOI":"10.1016\/S01406736(23)01473-3"},{"key":"3051_CR71","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00401-016-1653-y","volume":"133","author":"T Kuhlmann","year":"2017","unstructured":"Kuhlmann T, Ludwin S, Prat A, Antel J, Br\u00fcck W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13\u201324. https:\/\/doi.org\/10.1007\/s00401-016-1653-y.","journal-title":"Acta Neuropathol"},{"key":"3051_CR72","doi-asserted-by":"publisher","unstructured":"Woo MS, Engler JB, Friese MA. The neuropathobiology of multiple sclerosis. Nat Rev Neurosci. 2024. p. 493\u2013513. https:\/\/doi.org\/10.1038\/s41583-024-00823-z","DOI":"10.1038\/s41583-024-00823-z"},{"key":"3051_CR73","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/ane.12650","volume":"134","author":"P H\u00e4m\u00e4l\u00e4inen","year":"2016","unstructured":"H\u00e4m\u00e4l\u00e4inen P, Rosti-Otaj\u00e4rvi E. Cognitive impairment in MS: rehabilitation approaches. Acta Neurol Scand. 2016;134:8\u201313. https:\/\/doi.org\/10.1111\/ane.12650.","journal-title":"Acta Neurol Scand"},{"key":"3051_CR74","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.3390\/cells10092236","volume":"10","author":"J Lier","year":"2021","unstructured":"Lier J, Streit WJ, Bechmann I. Beyond activation: characterizing microglial functional phenotypes. Cells. 2021;10:2236 https:\/\/doi.org\/10.3390\/cells10092236.","journal-title":"Cells"},{"key":"3051_CR75","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/biom11060837","volume":"11","author":"A Leuti","year":"2021","unstructured":"Leuti A, Talamonti E, Gentile A, Tiberi M, Matteocci A, Fresegna D, et al. Macrophage plasticity and polarization are altered in the experimental model of multiple sclerosis. Biomolecules. 2021;11:837 https:\/\/doi.org\/10.3390\/biom11060837.","journal-title":"Biomolecules"},{"key":"3051_CR76","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1750-1326-3-13","volume":"3","author":"KJ Bryan","year":"2008","unstructured":"Bryan KJ, Zhu X, Harris PL, Perry G, Castellani RJ, Smith MA, et al. Expression of CD74 is increased in neurofibrillary tangles in Alzheimer\u2019s disease. Mol Neurodegener. 2008;3:13 https:\/\/doi.org\/10.1186\/1750-1326-3-13.","journal-title":"Mol Neurodegener"},{"key":"3051_CR77","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.cell.2019.11.026","volume":"180","author":"JY Lee","year":"2020","unstructured":"Lee JY, Hall JA, Kroehling L, Wu L, Najar T, Nguyen HH, et al. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell. 2020;180:79\u201391.e16. https:\/\/doi.org\/10.1016\/j.cell.2019.11.026.","journal-title":"Cell"},{"key":"3051_CR78","doi-asserted-by":"publisher","unstructured":"Scott-Hewitt N, Mahoney M, Huang Y, Korte N, Yvanka de Soysa T, Wilton DK, et al. Microglialderived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain. Cell. 2024;187:4193-4212.e24. https:\/\/doi.org\/10.1016\/j.cell.2024.05.058","DOI":"10.1016\/j.cell.2024.05.058"},{"key":"3051_CR79","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1111\/bpa.12546","volume":"28","author":"S Loveless","year":"2018","unstructured":"Loveless S, Neal JW, Howell OW, Harding KE, Sarkies P, Evans R, et al. Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis. Brain Pathol. 2018;28:507\u201320. https:\/\/doi.org\/10.1111\/bpa.12546.","journal-title":"Brain Pathol"},{"key":"3051_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0611-x","volume":"13","author":"LM Watkins","year":"2016","unstructured":"Watkins LM, Neal JW, Loveless S, Michailidou I, Ramaglia V, Rees MI, et al. Complement is activated in progressive multiple sclerosis cortical grey matter lesions. J Neuroinflamm. 2016;13:161. https:\/\/doi.org\/10.1186\/s12974-016-0611-x.","journal-title":"J Neuroinflamm"},{"key":"3051_CR81","doi-asserted-by":"publisher","unstructured":"Cooze BJ, Dickerson M, Loganathan R, Watkins LM, Grounds E, Pearson BR, et al. The association between neurodegeneration and local complement activation in the thalamus to progressive multiple sclerosis outcome. Brain Pathol. 2022;32. https:\/\/doi.org\/10.1111\/bpa.13054","DOI":"10.1111\/bpa.13054"},{"key":"3051_CR82","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1007\/s00415-019-09398-7","volume":"266","author":"L Gaetani","year":"2019","unstructured":"Gaetani L, Salvadori N, Lisetti V, Eusebi P, Mancini A, Gentili L, et al. Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. J Neurol. 2019;266:2157\u201363. https:\/\/doi.org\/10.1007\/s00415-019-09398-7.","journal-title":"J Neurol"},{"key":"3051_CR83","doi-asserted-by":"publisher","first-page":"105548","DOI":"10.1016\/j.msard.2024.105548","volume":"85","author":"L Gaetani","year":"2024","unstructured":"Gaetani L, Salvadori N, Brachelente G, Sperandei S, Di Sabatino E, Fiacca A, et al. Intrathecal B cell activation and memory impairment in multiple sclerosis. Mult Scler Relat Disord. 2024;85:105548 https:\/\/doi.org\/10.1016\/j.msard.2024.105548.","journal-title":"Mult Scler Relat Disord"},{"key":"3051_CR84","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200361","volume":"12","author":"J Oechtering","year":"2025","unstructured":"Oechtering J, Schaedelin SA, Stein K, Maleska Maceski A, Melie-Garcia L, Benkert P, et al. Aberrant complement activation is associated with structural brain damage in multiple sclerosis. Neurol(R) Neuroimmunol Neuroinflamm. 2025;12:e200361. https:\/\/doi.org\/10.1212\/NXI.0000000000200361.","journal-title":"Neurol(R) Neuroimmunol Neuroinflamm"},{"key":"3051_CR85","doi-asserted-by":"publisher","unstructured":"Adinolfi A, Di Sante G, Rivignani Vaccari L, Tredicine M, Ria F, Bonvissuto D, et al. Regionally restricted modulation of Sam68 expression and Arhgef9 alternative splicing in the hippocampus of a murine model of multiple sclerosis. Front Mol Neurosci. 2023;15. https:\/\/doi.org\/10.3389\/fnmol.2022.1073627","DOI":"10.3389\/fnmol.2022.1073627"},{"key":"3051_CR86","doi-asserted-by":"publisher","first-page":"748","DOI":"10.3390\/cells9030748","volume":"9","author":"G Di Sante","year":"2020","unstructured":"Di Sante G, Amadio S, Sampaolese B, Clementi ME, Valentini M, Volont\u00e9 C, et al. The S100B inhibitor pentamidine ameliorates clinical score and neuropathology of relapsing\u2013remitting multiple sclerosis mouse model. Cells. 2020;9:748 https:\/\/doi.org\/10.3390\/cells9030748.","journal-title":"Cells"},{"key":"3051_CR87","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.devcel.2017.03.003","volume":"41","author":"C Naro","year":"2017","unstructured":"Naro C, Jolly A, Di Persio S, Bielli P, Setterblad N, Alberdi AJ, et al. An orchestrated intron retention program in meiosis controls timely usage of transcripts during germ cell differentiation. Dev Cell. 2017;41:82\u201393.e4. https:\/\/doi.org\/10.1016\/j.devcel.2017.03.003.","journal-title":"Dev Cell"},{"key":"3051_CR88","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114751","volume":"43","author":"C Caggiano","year":"2024","unstructured":"Caggiano C, Petrera V, Ferri M, Pieraccioli M, Cesari E, Di Leone A, et al. Transient splicing inhibition causes persistent DNA damage and chemotherapy vulnerability in triple-negative breast cancer. Cell Rep. 2024;43:114751. https:\/\/doi.org\/10.1016\/j.celrep.2024.114751.","journal-title":"Cell Rep"},{"key":"3051_CR89","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545\u201350. https:\/\/doi.org\/10.1073\/pnas.0506580102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3051_CR90","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1212\/WNL.0b013e3181c47cc2","volume":"73","author":"CE Teunissen","year":"2009","unstructured":"Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology. 2009;73:1914\u201322. https:\/\/doi.org\/10.1212\/WNL.0b013e3181c47cc2.","journal-title":"Neurology"},{"key":"3051_CR91","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162\u201373. https:\/\/doi.org\/10.1016\/S1474-4422(17)30470-2.","journal-title":"Lancet Neurol"},{"key":"3051_CR92","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1212\/WNL.41.5.685","volume":"41","author":"SM Rao","year":"1991","unstructured":"Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology. 1991;41:685\u201391. https:\/\/doi.org\/10.1212\/WNL.41.5.685.","journal-title":"Neurology"},{"key":"3051_CR93","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1177\/1352458506070933","volume":"12","author":"MP Amato","year":"2006","unstructured":"Amato MP, Portaccio E, Goretti B, Zipoli V, Ricchiuti L, De Caro MF, et al. The Rao\u2019s brief repeatable battery and stroop test: normative values with age, education and gender corrections in an Italian population. Mult Scler. 2006;12:787\u201393. https:\/\/doi.org\/10.1177\/1352458506070933.","journal-title":"Mult Scler"},{"key":"3051_CR94","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1177\/1352458516674367","volume":"23","author":"L Ruano","year":"2017","unstructured":"Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, et al. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler. 2017;23:1258\u201367. https:\/\/doi.org\/10.1177\/1352458516674367.","journal-title":"Mult Scler"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03051-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03051-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03051-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:26:50Z","timestamp":1774985210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03051-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":94,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3051"],"URL":"https:\/\/doi.org\/10.1038\/s41420-026-03051-9","relation":{},"ISSN":["2058-7716"],"issn-type":[{"value":"2058-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"6 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All the authors have approved the final version of the manuscript and provided their consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"177"}}