Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5630191 | Journal of Neuroimmunology | 2017 | 6 Pages |
â¢Astrocyte-targeted production of IL-6 induced a specific microglial cell phenotype (Iba1+, CD11b+, MHCII+, CD68â).â¢Such microglia were less responsive to cuprizone-induced oligodendrocyte toxicity.â¢Consequently, demyelination was reduced in mice with astrocyte-targeted production of IL-6.
BackgroundCerebellar 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.ResultsOver 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 4-6Â weeks of cuprizone treatment, however after the chronic cuprizone treatment (12Â 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.ConclusionsOur 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+, CD68â), likely rendering them less responsive to subsequent injury signals.
Graphical abstractDownload high-res image (139KB)Download full-size image