PMID- 23161705 OWN - NLM STAT- MEDLINE DCOM- 20130530 LR - 20211021 IS - 1097-4547 (Electronic) IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 91 IP - 2 DP - 2013 Feb TI - N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum. PG - 240-8 LID - 10.1002/jnr.23150 [doi] 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 beta-amyloid precursor protein (beta-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in beta-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. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Zhang, Jingdong AU - Zhang J AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA. FAU - Liu, Jianuo AU - Liu J FAU - Fox, Howard S AU - Fox HS FAU - Xiong, Huangui AU - Xiong H LA - eng GR - P30 MH062261/MH/NIMH NIH HHS/United States GR - R01 NS063878/NS/NINDS NIH HHS/United States GR - R01 NS077873/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20121114 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Excitatory Amino Acids) RN - 0 (Myelin Basic Protein) RN - 0 (NMDA receptor A1) RN - 0 (Neuroprotective Agents) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 3KX376GY7L (Glutamic Acid) RN - 6LR8C1B66Q (Dizocilpine Maleate) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) SB - IM MH - Action Potentials/drug effects MH - Amyloid beta-Protein Precursor/metabolism MH - Animals MH - Axons/*pathology MH - Corpus Callosum/*metabolism MH - Disease Models, Animal MH - Dizocilpine Maleate/pharmacology MH - Excitatory Amino Acids/toxicity MH - Female MH - Glutamic Acid/toxicity MH - In Vitro Techniques MH - Male MH - Myelin Basic Protein/metabolism MH - Nerve Fibers, Myelinated/pathology/physiology MH - Neurons/metabolism MH - Neuroprotective Agents/pharmacology MH - Neurotoxicity Syndromes/etiology/*pathology MH - Oligodendroglia/metabolism MH - Patch-Clamp Techniques MH - Phosphopyruvate Hydratase/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*metabolism PMC - PMC3546500 MID - NIHMS432447 EDAT- 2012/11/20 06:00 MHDA- 2013/06/01 06:00 PMCR- 2014/02/01 CRDT- 2012/11/20 06:00 PHST- 2012/05/05 00:00 [received] PHST- 2012/08/31 00:00 [revised] PHST- 2012/09/07 00:00 [accepted] PHST- 2012/11/20 06:00 [entrez] PHST- 2012/11/20 06:00 [pubmed] PHST- 2013/06/01 06:00 [medline] PHST- 2014/02/01 00:00 [pmc-release] AID - 10.1002/jnr.23150 [doi] PST - ppublish SO - J Neurosci Res. 2013 Feb;91(2):240-8. doi: 10.1002/jnr.23150. Epub 2012 Nov 14.