title: Disruption of NMDA receptors in oligodendroglial lineage cells does not alter their susceptibility to experimental autoimmune encephalomyelitis or their normal development.
abstract: Pharmacological studies have suggested that oligodendroglial NMDA glutamate receptors (NMDARs) mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), a model of human MS, by timed conditional disruption of oligodendroglial NR1, an essential subunit of functional NMDARs, using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system. We found that selective ablation of oligodendroglial NR1 did not alter the clinical severity of EAE elicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1 KO and non-KO mice in numbers of axons lost in spinal cord dorsal funiculi or severity of spinal cord demyelination. Similarly, constitutive deletion of NR3A, a modulatory subunit of oligodendroglial NMDARs, did not alter the course of MOG-peptide EAE. Furthermore, conditional and constitutive ablation of NR1 in neonatal oligodendrocyte progenitor cells did not interrupt their normal maturation and differentiation. Collectively, our data suggest that oligodendroglial lineage NMDARs are neither required for timely postnatal development of the oligodendroglial lineage, nor significant participants in the pathophysiology of MOG-peptide EAE.
authors.affiliation: Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, California 95817, USA.
authors.forename: Fuzheng
authors.initials: F
authors.lastname: Guo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maeda
authors.forename: Emily Mills
authors.initials: EM
authors.lastname: Ko
authors.forename: Monica
authors.initials: M
authors.lastname: Delgado
authors.forename: Makoto
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Athena
authors.initials: A
authors.lastname: Soulika
authors.forename: Laird
authors.initials: L
authors.lastname: Miers
authors.forename: Travis
authors.initials: T
authors.lastname: Burns
authors.forename: Takayuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.forename: Jiho
authors.initials: J
authors.lastname: Sohn
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage / Q000502:physiology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C409466:NR1 NMDA receptor; C464437:NR3A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate