Local glucocorticoid synthesis and receptor signaling in cerebellar demyelination during canine distemper virus infection.

Canine distemper virus (CDV) induces central nervous system (CNS) demyelination, potentially influenced by local glucocorticoid metabolism via 11β-HSD enzymes and glucocorticoid receptors (GR). This study investigated the relationship between demyelination and local glucocorticoid synthesis in CDV infection. Cerebellar tissues from CDV-infected dogs (diseased group; n = 20) and clinically healthy dogs (control group; n = 10) were analyzed. Sections were immunohistochemically stained with anti-CDV, anti-11β-HSD1, anti-11β-HSD2, and anti-GR antibodies. In the diseased group, 11β-HSD1 immunopositivity was significantly higher than in controls in endothelial cells (p < 0.01), reactive astrocytes (p < 0.001), Purkinje neurons (p < 0.01), and molecular layer neurons (p < 0.001). 11β-HSD2 immunopositivity was significantly increased in reactive astrocytes (p < 0.01), white matter neurons (p < 0.001), and Purkinje neurons (p < 0.01). GR immunopositivity was elevated in reactive astrocytes (p < 0.01) and mossy fibers (p < 0.001). A strong positive correlation was observed between demyelination severity and 11β-HSD1 in reactive astrocytes (r = 0.915, p < 0.01), whereas a moderate negative correlation was found between demyelination severity and GR in reactive astrocytes (r = -0.461, p < 0.05). These findings indicate that local glucocorticoid metabolism is associated with CNS demyelination during CDV infection. This study provides novel insights into 11β-HSD enzymes and GR in CNS pathology, offering a translational model for understanding local glucocorticoid regulation in human demyelinating diseases such as multiple sclerosis.