Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes
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Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes R. Moreno-Luna 1 & P. F. Esteban 1 & B. Paniagua-Torija 1 & A. Arevalo-Martin 1 & D. Garcia-Ovejero 1 E. Molina-Holgado 1
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Received: 27 July 2020 / Accepted: 22 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In the last years, regional differences have been reported between the brain and spinal cord oligodendrocytes, which should be considered when designing therapeutic strategies for myelin repair. Promising targets to achieve myelin restoration are the different components of the endocannabinoid system (ECS) that modulate oligodendrocyte biology, but almost all studies have been focused on brain-derived cells. Therefore, we compared the ECS between the spinal cord and cerebral cortex-derived oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (OLs). Cells from both regions express synthesizing and degrading enzymes for the endocannabinoid 2arachidonoylglycerol, and degrading enzymes increase with maturation, more notably in the spinal cord (monoglyceride lipaseMGLL, alpha/beta hydrolase domain-containing 6-ABHD6, and alpha/beta hydrolase domain-containing 12-ABHD12). In addition, spinal cord OPCs express higher levels of the synthesizing enzymes diacylglycerol lipases alpha (DAGLA) and beta (DAGLB) than cortical ones, DAGLA reaching statistical significance. Cells from both the cortex and spinal cord express low levels of NAEs synthesizing enzymes, except for the glycerophosphodiester phosphodiesterase 1 (GDE-1) but high levels of the degrading enzyme fatty acid amidohydrolase (FAAH) that increases with maturation. Finally, cells from both regions show similar levels of CB1 receptor and GPR55, but spinal cord-derived cells show significantly higher levels of transient receptor potential cation channel V1 (TRPV1) and CB2. Overall, our results show that the majority of the ECS components could be targeted in OPCs and OLs from both the spinal cord and brain, but regional heterogeneity has to be considered for DAGLA, MGLL, ABHD6, ABHD12, GDE1, CB2, or TRPV1. Keywords Heterogeneity . Oligodendrocytes . Myelin . Cannabinoid . Spinal cord . High yield
Introduction Oligodendrocytes are the myelinating cells in the central nervous system (CNS). First described by del Rio Hortega [1], many aspects of their biology and their roles in health and disease have D. Garcia-Ovejero and E. Molina-Holgado should be considered joint senior and corresponding authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02148-1) contains supplementary material, which is available to authorized users. * D. Garcia-Ovejero [email protected] * E. Molina-Holgado [email protected] R. Moreno-Luna https://orcid.org/0000-0001-6693-1682 1
Laboratory of Neuroinflammation (lab i2 06), Hospital Nacional de Paraplejicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain
been deciphered in the last decades, such as the st
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