Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis
Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, b...
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doaj-3dd0beb770d544cc898258b26776a28d2020-11-25T03:19:41ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0191681168110.3390/jcm9061681Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple SclerosisAna Bribián0Eva M. Medina-Rodríguez1Fernando Josa-Prado2Isabel García-Álvarez3Isabel Machín-Díaz4Pedro F. Esteban5Verónica Murcia-Belmonte6Lorena Vega-Zelaya7Jesús Pastor8Leoncio Garrido9Fernando de Castro10Instituto Cajal-CSIC, CSIC, Avda. Dr. Arce 37, 28002 Madrid, SpainGrupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, 45071 Toledo, SpainInstituto Cajal-CSIC, CSIC, Avda. Dr. Arce 37, 28002 Madrid, SpainFacultad de Ciencias Experimentales, Universidad Francisco de Vitoria, Ctra. Pozuelo-Majadahonda Km 1800, Pozuelo de Alarcón, 28223 Madrid, SpainGrupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, 45071 Toledo, SpainGrupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, 45071 Toledo, SpainGrupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, 45071 Toledo, SpainNeurofisiología Clínica; Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, 28006 Madrid, SpainNeurofisiología Clínica; Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, 28006 Madrid, SpainInstituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), CSIC, Juan de la Cierva 3, 28006 Madrid, SpainInstituto Cajal-CSIC, CSIC, Avda. Dr. Arce 37, 28002 Madrid, SpainBesides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS.https://www.mdpi.com/2077-0383/9/6/1681oligodendrocytemyelinmultiple sclerosishumanremyelinationleukodystrophies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Bribián Eva M. Medina-Rodríguez Fernando Josa-Prado Isabel García-Álvarez Isabel Machín-Díaz Pedro F. Esteban Verónica Murcia-Belmonte Lorena Vega-Zelaya Jesús Pastor Leoncio Garrido Fernando de Castro |
spellingShingle |
Ana Bribián Eva M. Medina-Rodríguez Fernando Josa-Prado Isabel García-Álvarez Isabel Machín-Díaz Pedro F. Esteban Verónica Murcia-Belmonte Lorena Vega-Zelaya Jesús Pastor Leoncio Garrido Fernando de Castro Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis Journal of Clinical Medicine oligodendrocyte myelin multiple sclerosis human remyelination leukodystrophies |
author_facet |
Ana Bribián Eva M. Medina-Rodríguez Fernando Josa-Prado Isabel García-Álvarez Isabel Machín-Díaz Pedro F. Esteban Verónica Murcia-Belmonte Lorena Vega-Zelaya Jesús Pastor Leoncio Garrido Fernando de Castro |
author_sort |
Ana Bribián |
title |
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis |
title_short |
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis |
title_full |
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis |
title_fullStr |
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis |
title_full_unstemmed |
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis |
title_sort |
functional heterogeneity of mouse and human brain opcs: relevance for preclinical studies in multiple sclerosis |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-06-01 |
description |
Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS. |
topic |
oligodendrocyte myelin multiple sclerosis human remyelination leukodystrophies |
url |
https://www.mdpi.com/2077-0383/9/6/1681 |
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