N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum

Jingdong Zhang, Jianuo Liu, Howard S Fox, Huangui Xiong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input-output response. Both Glut and NMDA decreased the CAP amplitude and input-output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro.

Original languageEnglish (US)
Pages (from-to)240-248
Number of pages9
JournalJournal of Neuroscience Research
Volume91
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Corpus Callosum
N-Methyl-D-Aspartate Receptors
Wounds and Injuries
Glutamic Acid
Oligodendroglia
N-Methylaspartate
Axonal Transport
Action Potentials
Western Blotting
Myelinated Nerve Fibers
AMPA Receptors
Amyloid beta-Protein Precursor
Brain Diseases
Carisoprodol
Myelin Sheath
Staining and Labeling

Keywords

  • Corpus callosum
  • Excitotoxicity
  • Myelinated fibers
  • NMDA receptor
  • Oligodendrocyte

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum. / Zhang, Jingdong; Liu, Jianuo; Fox, Howard S; Xiong, Huangui.

In: Journal of Neuroscience Research, Vol. 91, No. 2, 01.02.2013, p. 240-248.

Research output: Contribution to journalArticle

@article{293bbd64b17b40449c3379bdc6808222,
title = "N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum",
abstract = "Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input-output response. Both Glut and NMDA decreased the CAP amplitude and input-output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro.",
keywords = "Corpus callosum, Excitotoxicity, Myelinated fibers, NMDA receptor, Oligodendrocyte",
author = "Jingdong Zhang and Jianuo Liu and Fox, {Howard S} and Huangui Xiong",
year = "2013",
month = "2",
day = "1",
doi = "10.1002/jnr.23150",
language = "English (US)",
volume = "91",
pages = "240--248",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum

AU - Zhang, Jingdong

AU - Liu, Jianuo

AU - Fox, Howard S

AU - Xiong, Huangui

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input-output response. Both Glut and NMDA decreased the CAP amplitude and input-output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro.

AB - Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input-output response. Both Glut and NMDA decreased the CAP amplitude and input-output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro.

KW - Corpus callosum

KW - Excitotoxicity

KW - Myelinated fibers

KW - NMDA receptor

KW - Oligodendrocyte

UR - http://www.scopus.com/inward/record.url?scp=84870910970&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870910970&partnerID=8YFLogxK

U2 - 10.1002/jnr.23150

DO - 10.1002/jnr.23150

M3 - Article

VL - 91

SP - 240

EP - 248

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 2

ER -