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Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate

The severe motor impairment in the MS animal model experimental autoimmune encephalomyelitis (EAE) obstructs the assessment of cognitive functions. We developed an experimental system that evaluates memory faculties in EAE-affected mice, irrespective of their motor performance, enabling the assessme...

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Autores principales: Aharoni, Rina, Schottlender, Nofar, Bar-Lev, Dekel D., Eilam, Raya, Sela, Michael, Tsoory, Michael, Arnon, Ruth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412002/
https://www.ncbi.nlm.nih.gov/pubmed/30858445
http://dx.doi.org/10.1038/s41598-019-40713-4
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author Aharoni, Rina
Schottlender, Nofar
Bar-Lev, Dekel D.
Eilam, Raya
Sela, Michael
Tsoory, Michael
Arnon, Ruth
author_facet Aharoni, Rina
Schottlender, Nofar
Bar-Lev, Dekel D.
Eilam, Raya
Sela, Michael
Tsoory, Michael
Arnon, Ruth
author_sort Aharoni, Rina
collection PubMed
description The severe motor impairment in the MS animal model experimental autoimmune encephalomyelitis (EAE) obstructs the assessment of cognitive functions. We developed an experimental system that evaluates memory faculties in EAE-affected mice, irrespective of their motor performance, enabling the assessment of cognitive impairments along the disease duration, the associated brain damage, and the consequences of glatiramer acetate (GA) treatment on these manifestations. The delayed-non-matching to sample (DNMS) T-maze task, testing working and long term memory was adapted and utilized. Following the appearance of clinical manifestations task performances of the EAE-untreated mice drastically declined. Cognitive impairments were associated with disease severity, as indicated by a significant correlation between the T-maze performance and the clinical symptoms in EAE-untreated mice. GA-treatment conserved cognitive functions, so that despite their exhibited mild motor impairments, the treated mice performed similarly to naïve controls. The cognitive deficit of EAE-mice coincided with inflammatory and neurodegenerative damage to the frontal cortex and the hippocampus; these damages were alleviated by GA-treatment. These combined findings indicate that in addition to motor impairment, EAE leads to substantial impairment of cognitive functions, starting at the early stages and increasing with disease aggravation. GA-treatment, conserves cognitive capacities and prevents its disease related deterioration.
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spelling pubmed-64120022019-03-13 Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate Aharoni, Rina Schottlender, Nofar Bar-Lev, Dekel D. Eilam, Raya Sela, Michael Tsoory, Michael Arnon, Ruth Sci Rep Article The severe motor impairment in the MS animal model experimental autoimmune encephalomyelitis (EAE) obstructs the assessment of cognitive functions. We developed an experimental system that evaluates memory faculties in EAE-affected mice, irrespective of their motor performance, enabling the assessment of cognitive impairments along the disease duration, the associated brain damage, and the consequences of glatiramer acetate (GA) treatment on these manifestations. The delayed-non-matching to sample (DNMS) T-maze task, testing working and long term memory was adapted and utilized. Following the appearance of clinical manifestations task performances of the EAE-untreated mice drastically declined. Cognitive impairments were associated with disease severity, as indicated by a significant correlation between the T-maze performance and the clinical symptoms in EAE-untreated mice. GA-treatment conserved cognitive functions, so that despite their exhibited mild motor impairments, the treated mice performed similarly to naïve controls. The cognitive deficit of EAE-mice coincided with inflammatory and neurodegenerative damage to the frontal cortex and the hippocampus; these damages were alleviated by GA-treatment. These combined findings indicate that in addition to motor impairment, EAE leads to substantial impairment of cognitive functions, starting at the early stages and increasing with disease aggravation. GA-treatment, conserves cognitive capacities and prevents its disease related deterioration. Nature Publishing Group UK 2019-03-11 /pmc/articles/PMC6412002/ /pubmed/30858445 http://dx.doi.org/10.1038/s41598-019-40713-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Aharoni, Rina
Schottlender, Nofar
Bar-Lev, Dekel D.
Eilam, Raya
Sela, Michael
Tsoory, Michael
Arnon, Ruth
Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title_full Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title_fullStr Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title_full_unstemmed Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title_short Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
title_sort cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412002/
https://www.ncbi.nlm.nih.gov/pubmed/30858445
http://dx.doi.org/10.1038/s41598-019-40713-4
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