Brain inflammation is accompanied by peripheral inflammation in Cstbmice, a model for progressive myoclonus epilepsy.

Abstract

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstbmice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstbmice and higher CXCL13 expression in activated microglia in Cstbcompared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstbmice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstbmice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.