Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study

Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study

Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800) is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin...

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Main Authors: Manninen, Otto, Laitinen, Teemu, Lehtimäki, Kimmo K., Tegelberg, Saara, Lehesjoki, Anna-Elina, Gröhn, Olli, Kopra, Outi
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948351/
id pubmed-3948351
recordtype oai_dc
spelling pubmed-39483512014-03-13 Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study Manninen, Otto Laitinen, Teemu Lehtimäki, Kimmo K. Tegelberg, Saara Lehesjoki, Anna-Elina Gröhn, Olli Kopra, Outi Research Article Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800) is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin B. Previously, widespread white matter changes and atrophy has been detected both in adult EPM1 patients and in 6-month-old cystatin B–deficient mice, a mouse model for the EPM1 disease. In order to elucidate the spatiotemporal dynamics of the brain atrophy and white matter changes in EPM1, we conducted longitudinal in vivo magnetic resonance imaging and ex vivo diffusion tensor imaging accompanied with tract-based spatial statistics analysis to compare volumetric changes and fractional anisotropy in the brains of 1 to 6 months of age cystatin B–deficient and control mice. The results reveal progressive but non-uniform volume loss of the cystatin B–deficient mouse brains, indicating that different neuronal populations possess distinct sensitivity to the damage caused by cystatin B deficiency. The diffusion tensor imaging data reveal early and progressive white matter alterations in cystatin B–deficient mice affecting all major tracts. The results also indicate that the white matter damage in the cystatin B–deficient brain is most likely secondary to glial activation and neurodegenerative events rather than a primary result of CSTB deficiency. The data also show that diffusion tensor imaging combined with TBSS analysis provides a feasible approach not only to follow white matter damage in neurodegenerative mouse models but also to detect fractional anisotropy changes related to normal white matter maturation and reorganisation. Public Library of Science 2014-03-06 /pmc/articles/PMC3948351/ /pubmed/24603771 http://dx.doi.org/10.1371/journal.pone.0090709 Text en © 2014 Manninen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Manninen, Otto
Laitinen, Teemu
Lehtimäki, Kimmo K.
Tegelberg, Saara
Lehesjoki, Anna-Elina
Gröhn, Olli
Kopra, Outi
spellingShingle Manninen, Otto
Laitinen, Teemu
Lehtimäki, Kimmo K.
Tegelberg, Saara
Lehesjoki, Anna-Elina
Gröhn, Olli
Kopra, Outi
Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
author_facet Manninen, Otto
Laitinen, Teemu
Lehtimäki, Kimmo K.
Tegelberg, Saara
Lehesjoki, Anna-Elina
Gröhn, Olli
Kopra, Outi
author_sort Manninen, Otto
title Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
title_short Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
title_full Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
title_fullStr Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
title_full_unstemmed Progressive Volume Loss and White Matter Degeneration in Cstb-Deficient Mice: A Diffusion Tensor and Longitudinal Volumetry MRI Study
title_sort progressive volume loss and white matter degeneration in cstb-deficient mice: a diffusion tensor and longitudinal volumetry mri study
description Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1, OMIM 254800) is an autosomal recessive disorder characterized by onset at the age of 6 to 16 years, incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures. It is caused by mutations in the gene encoding cystatin B. Previously, widespread white matter changes and atrophy has been detected both in adult EPM1 patients and in 6-month-old cystatin B–deficient mice, a mouse model for the EPM1 disease. In order to elucidate the spatiotemporal dynamics of the brain atrophy and white matter changes in EPM1, we conducted longitudinal in vivo magnetic resonance imaging and ex vivo diffusion tensor imaging accompanied with tract-based spatial statistics analysis to compare volumetric changes and fractional anisotropy in the brains of 1 to 6 months of age cystatin B–deficient and control mice. The results reveal progressive but non-uniform volume loss of the cystatin B–deficient mouse brains, indicating that different neuronal populations possess distinct sensitivity to the damage caused by cystatin B deficiency. The diffusion tensor imaging data reveal early and progressive white matter alterations in cystatin B–deficient mice affecting all major tracts. The results also indicate that the white matter damage in the cystatin B–deficient brain is most likely secondary to glial activation and neurodegenerative events rather than a primary result of CSTB deficiency. The data also show that diffusion tensor imaging combined with TBSS analysis provides a feasible approach not only to follow white matter damage in neurodegenerative mouse models but also to detect fractional anisotropy changes related to normal white matter maturation and reorganisation.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948351/
_version_ 1612066016941047808

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