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Temporal and Spatial Dynamics of Astroglial Reaction and Immune Response in Cuprizone-Induced Demyelination
- Source :
- Neurotoxicity Research. 37:587-601
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- The cuprizone (CPZ)-induced demyelination is a relatively reproducible animal model and has been extremely useful for identifying the specific cellular and molecular signals that regulate oligodendrocyte survival and efficiency of oligodendrogenesis and remyelination. Here, we reported the temporal and spatial dynamics of astroglial reaction and immune response in CPZ-induced demyelinating model. CPZ did not induce significant microglia and astrocyte reaction after 2 weeks of feeding. After 4-6 weeks of CPZ feeding, microglia and astrocytes were markedly migrated and accumulated in myelin sheath. Simultaneously, the expression of tight junction protein ZO-1 was declined and the infiltration of CD4+IFNγ+ and CD4+IL-17+ T cells was increased in the brain, accompanied by increased production of IFN-γ and IL-17 in the extract of brain. However, the levels of IFN-γ and IL-17 were reduced, while IL-6 and TNF-α were elevated in the supernatant of splenocytes. At the 4th and 6th weeks of feeding, CPZ caused astrocyte activation and upregulated the expression of BDNF, CNTF, and IGF-II, providing a neurotrophic microenvironment in the brain. At this stage, NG2+ and PDGF-Rα+ oligodendroglia progenitor cells were enhanced in the corpus callosum, but the myelin sheath is still severely lost. Therefore, targeting microglia to improve the inflammatory microenvironment should contribute to the remyelination.
- Subjects :
- 0301 basic medicine
Microglia
biology
Chemistry
General Neuroscience
Ciliary neurotrophic factor
Toxicology
Oligodendrocyte
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Immune system
nervous system
medicine
biology.protein
Progenitor cell
Remyelination
030217 neurology & neurosurgery
Astrocyte
Neurotrophin
Subjects
Details
- ISSN :
- 14763524 and 10298428
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi...........2b10b86b454bea5192acdafef97f120c