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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianuo
authors.initials: J
authors.lastname: Liu
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000473:pathology*; D003337:Corpus Callosum / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000633:toxicity; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016291:Dizocilpine Maleate; D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D010751:Phosphopyruvate Hydratase; D016194:Receptors, N-Methyl-D-Aspartate