期刊
HISTOCHEMISTRY AND CELL BIOLOGY
卷 158, 期 1, 页码 15-38出版社
SPRINGER
DOI: 10.1007/s00418-022-02096-y
关键词
Multiple sclerosis; Demyelination; Astrocytes; Cuprizone
资金
- Genzyme Neuroimmunology Fellowship
The loss of myelin, degeneration of axons, and impaired remyelination contribute to the progressive disease in multiple sclerosis patients. Astrocytes play a vital role in these processes. Our study identified GFAP, vimentin, LCN2, and ALDH1L1 as reliable markers for activated astrocytes during cuprizone-induced de- and remyelination.
Myelin loss with consecutive axon degeneration and impaired remyelination are the underlying causes of progressive disease in patients with multiple sclerosis. Astrocytes are suggested to play a major role in these processes. The unmasking of distinct astrocyte identities in health and disease would help to understand the pathophysiological mechanisms in which astrocytes are involved. However, the number of specific astrocyte markers is limited. Therefore, we performed immunohistochemical studies and analyzed various markers including GFAP, vimentin, S100B, ALDH1L1, and LCN2 during de- and remyelination using the toxic murine cuprizone animal model. Applying this animal model, we were able to confirm overlapping expression of vimentin and GFAP and highlighted the potential of ALDH1L1 as a pan-astrocytic marker, in agreement with previous data. Only a small population of GFAP-positive astrocytes in the corpus callosum highly up-regulated LCN2 at the peak of demyelination and S100B expression was found in a subset of oligodendroglia as well, thus S100B turned out to have a limited use as a particular astroglial marker. Additionally, numerous GFAP-positive astrocytes in the lateral corpus callosum did not express S100B, further strengthening findings of heterogeneity in the astrocytic population. In conclusion, our results acknowledged that GFAP, vimentin, LCN2, and ALDH1L1 serve as reliable marker to identify activated astrocytes during cuprizone-induced de- and remyelination. Moreover, there were clear regional and temporal differences in protein and mRNA expression levels and patterns of the studied markers, generally between gray and white matter structures.
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