Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia
2017
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2017 Published by Elsevier B.V.
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
Neuroinflammation; Demyelination; Interleukin-6; Microglia; Multiple sclerosis; CuprizoneФинансирање / пројекти:
- Spanish Ministry of Economy and Competitiveness (BFU2014-55459P)
У:
- Journal of Neuroimmunology (2017), 310: 97-102
DOI: 10.1016/j.jneuroim.2017.07.003
ISSN: 0165-5728
PubMed: 28778453
Scopus: 2-s2.0-85022182920
URI
http://linkinghub.elsevier.com/retrieve/pii/S0165572817301637https://radar.ibiss.bg.ac.rs/handle/123456789/2802