1. Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis
- Author
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Isabel García-Álvarez, E. M. Medina-Rodríguez, Leoncio Garrido, Jesús Pastor, Ana Bribián, Verónica Murcia-Belmonte, Pedro F. Esteban, Lorena Vega-Zelaya, Fernando Josa-Prado, Isabel Machín-Díaz, Fernando de Castro, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Red Española de Esclerosis Múltiple, Fundación Ramón Areces, and Fundación Eugenio Rodríguez Pascual
- Subjects
Central nervous system ,Cell ,lcsh:Medicine ,multiple sclerosis ,Article ,Leukodystrophies ,Multiple sclerosis ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine ,human ,Remyelination ,030304 developmental biology ,0303 health sciences ,leukodystrophies ,business.industry ,lcsh:R ,General Medicine ,Human brain ,medicine.disease ,Oligodendrocyte ,stomatognathic diseases ,myelin ,medicine.anatomical_structure ,remyelination ,nervous system ,Cerebral cortex ,demyelination ,Demyelination ,business ,Neuroscience ,030217 neurology & neurosurgery ,oligodendrocyte - Abstract
This article belongs to the Special Issue Glial Cells in Central Nervous System (CNS) Pathology and Repair., 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., This research was funded by the Spanish Ministerio de Ciencia, Innovación y Universidades (former Ministerio de Economía y Competitividad-MINECO: grant numbers SAF2009–07842, ADE10-0010, SAF2012-40023, SAF2016-77575-R, and the Red Española de Esclerosis Múltiple: RD12-0032-12; RD16/0015/0019), Spanish Research Council-CSIC (grant number PID2019-109858RB-100), the ‘‘Fundación Eugenio Rodríguez Pascual’’ (Spain) and the “Fundación Ramón Areces” (grant number CIVP19A5917). The APC was funded by grants SAF2016-77575-R and PID2019-109858RB-100.
- Published
- 2020