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Free keywords:
oligodendrocytes; glial-axonal interactions; white matter damage; glutamate receptors INTRAAXONAL NEUROFILAMENT COMPACTION; AMYLOID PRECURSOR PROTEIN; CEREBRAL WHITE-MATTER; SPINAL-CORD TRAUMA; GLUTAMATE-RECEPTOR; OLIGODENDROCYTE LINEAGE; AMPA/KAINATE RECEPTORS; MULTIPLE-SCLEROSIS; OPTIC-NERVE; CNS MYELIN
Abstract:
In vivo and in vitro studies have shown that alpha-amino-3hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor-mediated excitotoxicity causes cytoskeletal damage to axons. AMPA/kainate receptors are present on oligodendrocytes and myelin, but currently there is no evidence to suggest that axon cylinders contain AMPA receptors. Proteolipid protein (PLIP) and DM20 are integral membrane proteins expressed by CNS oligodendrocytes and located in compact myelin. Humans and mice lacking normal PLP/DM20 develop axonal swellings and degeneration, suggesting that local interactions between axons and the oligodendrocyte/myelin unit are important for the normal functioning of axons and that PLP/DM20 is involved in this process. To determine whether perturbed glial-axonal interaction affects AMPA-receptor-mediated axonal damage, AMPA (1.5 nmol) was injected into the caudate nucleus of anesthetized Pip knockout and wild-type male mice (n = 13). Twenty-four hours later, axonal damage was detected by using neurofilament 200 (NF 200) immunohistochemistry and neuronal damage detected via histology. AMPA-induced axonal damage, assessed with NF 200 immunohistochemistry, was significantly reduced in Plp knockout mice compared with wildtype mice (P = 0.015). There was no significant difference in the levels of neuronal perikaryal damage between the Plp knockout and wild-type mice. In addition, there was no significant difference in the levels of glutamate receptor subunits GluR1-4 or KA2 in Plp knockout compared with wild-type littermates. The present study suggests that PLP-mediated interactions among oligodendrocytes myelin, and axons may be involved in AMPA-mediate axonal damage. (c) 2006 Wiley-Liss, Inc.
