Temporal and Spatial Dynamics of Astroglial Reaction and Immune Response in Cuprizone-Induced Demyelination

Overview

Journal Neurotox Res

Publisher Springer

Specialty Neurology

Date 2019 Nov 14

PMID 31721051

Citations 9

Authors

Jun An

Jun-Jun Yin

Yan He

Ruo-Xuan Sui

Qiang Miao

Qing Wang

Jie-Zhong Yu

Jing-Wen Yu

Fu-Dong Shi

Cun-Gen Ma

Bao-Guo Xiao

Affiliations

Soon will be listed here.

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.

Citing Articles

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