Differential inductions of small heat shock protein 27 and 1‐Cys peroxiredoxin in reactive astrocytes in sulfatide‐deficient mouse spinal cord

Abstract

In myelinated fibers, various interactions among axons, oligodendrocytes, and astrocytes are present, particularly around the node of Ranvier. In the present study, we examined the protein composition of cerebroside sulfotransferase knockout (CST KO) mouse spinal cord by two-dimensional gel electrophoresis to examine the molecular changes resulting from the disruption of paranodal junctions in addition to the sulfatide-deficient condition. Interestingly, heat shock protein 27 (Hsp27) and 1-cys peroxiredoxin (1-Cys Prx) were both elevated in CST KO mice. Hsp27 was increased specifically in reactive astrocytes in the white matter, and the elevation was well correlated to the progression of neurologic symptoms. In contrast, 1-Cys Prx was elevated both in white and gray matter astrocytes in CST KO mice. These results suggest that astrocytes do not always respond stereotypically, as they display differences in their activation in these two regions. To determine whether these changes are specific to the sulfatide-deficient condition, spinal cords from CST KO mice and the hypomyelinating mutant shiverer mice were compared. The same distribution patterns of Hsp27 and 1-Cys Prx were found in reactive astrocytes in both CST KO and shiverer mice, suggesting that paranodal disruption with progressive nodal changes may underlie the similar reaction of white matter astrocytes. In contrast, CST KO and shiverer mice showed distinctly different localization patterns of connexin 43 and connexin 47, suggesting that intercellular communication between astrocytes and oligodendrocytes was different in these mutants. These results suggest that astrocytes may respond differentially to individual white matter abnormalities and may modulate specific axonal functions.