Expression of Kallikrein in Glial Cells and Its Influence on Oligodendrocyte Myelination

Abstract

Appropriate myelin structures are crucial for efficient nerve impulse conduction; however, the precise mechanisms sustaining myelin integrity throughout life remain unclear. KLK6 and KLK8 (Klk8 in mice), serine proteases of the tissue kallikrein family, are upregulated in oligodendrocytes in response to central nervous system injuries and are associated with myelin degradation. However, the physiological roles of these proteases have not yet been fully clarified. Here, we examined whether Klk8 and Klk6 are expressed in glial cells other than oligodendrocytes and whether Klk8 affects myelin structure under physiological conditions. Microglia, oligodendrocytes, and astrocytes were isolated from the brains and spinal cords of wild-type and Klk8 knockout mice, and we examined the expression levels of Klk8, Klk6, and myelin-related genes. We found that both Klk6 and Klk8 expression levels in oligodendrocytes were correlated with myelin-related gene expression levels. The myelin-related gene expression levels in oligodendrocytes were significantly higher in Klk8 knockout mice than in wild-type mice. Immunohistochemistry, western blotting, and transmission electron microscopy revealed that, compared with that in wild-type mice, the myelin volume and thickness were greater in Klk8 knockout mice. Oligodendrocyte-expressed Klk8 may play a role in modulating myelin structure under physiological conditions. Klk8 expression was higher in microglia than in oligodendrocytes, and Klk6 expression was higher in astrocytes than in oligodendrocytes. The expression levels of Klk6 and Klk8 in microglia and astrocytes were uncorrelated with the expression of myelin-related genes in oligodendrocytes, suggesting that these genes in microglia and astrocytes may have functional roles other than myelination.

Keywords: glial cell; kallikrein 8; myelination; oligodendrocyte.