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Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy

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 rec...

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Autores principales: Okuneva, Olesya, Li, Zhilin, Körber, Inken, Tegelberg, Saara, Joensuu, Tarja, Tian, Li, Lehesjoki, Anna-Elina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127053/
https://www.ncbi.nlm.nih.gov/pubmed/27894304
http://dx.doi.org/10.1186/s12974-016-0764-7
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author Okuneva, Olesya
Li, Zhilin
Körber, Inken
Tegelberg, Saara
Joensuu, Tarja
Tian, Li
Lehesjoki, Anna-Elina
author_facet Okuneva, Olesya
Li, Zhilin
Körber, Inken
Tegelberg, Saara
Joensuu, Tarja
Tian, Li
Lehesjoki, Anna-Elina
author_sort Okuneva, Olesya
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0764-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-51270532016-12-08 Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy Okuneva, Olesya Li, Zhilin Körber, Inken Tegelberg, Saara Joensuu, Tarja Tian, Li Lehesjoki, Anna-Elina J Neuroinflammation Short Report 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0764-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-28 /pmc/articles/PMC5127053/ /pubmed/27894304 http://dx.doi.org/10.1186/s12974-016-0764-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Okuneva, Olesya
Li, Zhilin
Körber, Inken
Tegelberg, Saara
Joensuu, Tarja
Tian, Li
Lehesjoki, Anna-Elina
Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title_full Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title_fullStr Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title_full_unstemmed Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title_short Brain inflammation is accompanied by peripheral inflammation in Cstb(−/−) mice, a model for progressive myoclonus epilepsy
title_sort brain inflammation is accompanied by peripheral inflammation in cstb(−/−) mice, a model for progressive myoclonus epilepsy
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127053/
https://www.ncbi.nlm.nih.gov/pubmed/27894304
http://dx.doi.org/10.1186/s12974-016-0764-7
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