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 ofEAEelicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1KO 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 639-645 |
| Number of pages | 7 |
| Journal | Journal of Neuroscience |
| Volume | 32 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 11 2012 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Disruption of NMDA receptors in oligodendroglial lineage cells does not alter their susceptibility to experimental autoimmune encephalomyelitis or their normal development. / Guo, Fuzheng; Maeda, Yoshiko; Ko, Emily Mills; Delgado, Monica; Horiuchi, Makoto; Soulika, Athena; Miers, Laird; Burns, Travis; Ito, Takayuki; Shen, Haitao; Lee, Eunyoung; Sohn, Jiho; Pleasure, David E.
In: Journal of Neuroscience, Vol. 32, No. 2, 11.01.2012, p. 639-645.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disruption of NMDA receptors in oligodendroglial lineage cells does not alter their susceptibility to experimental autoimmune encephalomyelitis or their normal development
AU - Guo, Fuzheng
AU - Maeda, Yoshiko
AU - Ko, Emily Mills
AU - Delgado, Monica
AU - Horiuchi, Makoto
AU - Soulika, Athena
AU - Miers, Laird
AU - Burns, Travis
AU - Ito, Takayuki
AU - Shen, Haitao
AU - Lee, Eunyoung
AU - Sohn, Jiho
AU - Pleasure, David E
PY - 2012/1/11
Y1 - 2012/1/11
N2 - 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 ofEAEelicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1KO 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.
AB - 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 ofEAEelicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1KO 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.
UR - http://www.scopus.com/inward/record.url?scp=84855702764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855702764&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4073-11.2012
DO - 10.1523/JNEUROSCI.4073-11.2012
M3 - Article
C2 - 22238099
AN - SCOPUS:84855702764
VL - 32
SP - 639
EP - 645
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 2
ER -