title: Brain inflammation is accompanied by peripheral inflammation in Cstb-/-mice, 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 Cstb-/-mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb-/-mice and higher CXCL13 expression in activated microglia in Cstb-/-compared 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 Cstb-/-mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb-/-mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.
authors.affiliation: Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00014, Helsinki, Finland.|Research Program's Unit, Molecular Neurology, University of Helsinki, Haartmaninkatu 8, 00014, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
authors.forename: Olesya
authors.initials: O
authors.lastname: Okuneva
authors.affiliation: Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00014, Helsinki, Finland. anna-elina.lehesjoki@helsinki.fi.|Research Program's Unit, Molecular Neurology, University of Helsinki, Haartmaninkatu 8, 00014, Helsinki, Finland. anna-elina.lehesjoki@helsinki.fi.|Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland. anna-elina.lehesjoki@helsinki.fi.
authors.forename: Inken
authors.initials: I
authors.lastname: Körber
authors.affiliation: Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00014, Helsinki, Finland.|Research Program's Unit, Molecular Neurology, University of Helsinki, Haartmaninkatu 8, 00014, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Tegelberg
authors.affiliation: Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00014, Helsinki, Finland.|Research Program's Unit, Molecular Neurology, University of Helsinki, Haartmaninkatu 8, 00014, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Joensuu
authors.affiliation: Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.|Beijing Huilongguan Hospital, Peking University teaching hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Folkhälsan Institute of Genetics, Haartmaninkatu 8, 00014, Helsinki, Finland.|Research Program's Unit, Molecular Neurology, University of Helsinki, Haartmaninkatu 8, 00014, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D055313:Cystatin B / Q000172:deficiency* / Q000235:genetics; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004660:Encephalitis / Q000097:blood / Q000209:etiology*; D005786:Gene Expression Regulation / Q000235:genetics*; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D020191:Myoclonic Epilepsies, Progressive / Q000150:complications* / Q000235:genetics*
chemical_list: C524992:Cstb protein, mouse; D016207:Cytokines; D055313:Cystatin B
keywords: CXCL13; Chemokine; Cystatin B; M1/M2; Macrophage; Vascularization