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Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia
dc.creator | Petković, Filip | |
dc.creator | Campbell, Iain L. | |
dc.creator | Gonzalez, Berta | |
dc.creator | Castellano, Bernardo | |
dc.date.accessioned | 2017-11-23T11:28:04Z | |
dc.date.available | 2900-01-01 | |
dc.date.issued | 2017 | |
dc.identifier.issn | 0165-5728 | |
dc.identifier.uri | http://linkinghub.elsevier.com/retrieve/pii/S0165572817301637 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/2802 | |
dc.description.abstract | Cerebellar pathology is a frequent feature of multiple sclerosis (MS), a demyelinating and neuroinflammatory disease of the central nervous system (CNS). Interleukin (IL)-6 is a multifunctional cytokine with a potential role in MS. Here we studied cuprizone-induced cerebellar pathology in transgenic mice with astrocyte-targeted production of IL-6 (GFAP-IL6), specifically focusing on demyelination, oligodendrocyte depletion and microglial cell response. Results Over the course of cuprizone treatment, when compared with WT mice, GFAP-IL6Tg showed a reduced demyelination in the deep lateral cerebellar nuclei (LCN). The oligodendrocyte numbers in the LCN were comparable between WT and GFAP-IL6Tg mice after 4–6 weeks of cuprizone treatment, however after the chronic cuprizone treatment (12 weeks) we detected higher numbers of oligodendrocytes in GFAP-IL6Tg mice. Contrary to strong cuprizone-induced microglial activation in the LCN of WT mice, GFAP-IL6Tg mice had minimal cuprizone-induced microglial changes, despite an already existing reactive microgliosis in control GFAP-IL6Tg not present in control WT mice. Conclusions Our results show that chronic transgenic production of IL-6 reduced cuprizone-induced cerebellar demyelination and induced a specific activation state of the resident microglia population (Iba1 + , CD11b + , MHCII + , CD68 − ), likely rendering them less responsive to subsequent injury signals. | en |
dc.relation | Spanish Ministry of Economy and Competitiveness (BFU2014-55459P) | |
dc.rights | restrictedAccess | |
dc.source | Journal of Neuroimmunology | |
dc.subject | Neuroinflammation | |
dc.subject | Demyelination | |
dc.subject | Interleukin-6 | |
dc.subject | Microglia | |
dc.subject | Multiple sclerosis | |
dc.subject | Cuprizone | |
dc.title | Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Цампбелл, Иаин Л.; Гонзалез, Берта; Цастеллано, Бернардо; Петковић, Филип; | |
dc.rights.holder | © 2017 Published by Elsevier B.V. | |
dc.citation.volume | 310 | |
dc.description.other | Journal of Neuroimmunology (2017), 310: 97-102 | |
dc.identifier.doi | 10.1016/j.jneuroim.2017.07.003 | |
dc.identifier.pmid | 28778453 | |
dc.identifier.scopus | 2-s2.0-85022182920 | |
dc.citation.apa | Petković, F., Campbell, I. L., Gonzalez, B., & Castellano, B. (2017). Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia. Journal of Neuroimmunology, 310, 97–102. | |
dc.citation.vancouver | Petković F, Campbell IL, Gonzalez B, Castellano B. Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia. J Neuroimmunol. 2017;310:97–102. | |
dc.citation.spage | 97 | |
dc.citation.epage | 102 | |
dc.type.version | publishedVersion | en |
dc.citation.rank | M22 |