Neurotrophin-3 (NT-3) diminishes susceptibility of the oligodendroglial lineage to AMPA glutamate receptor-mediated excitotoxicity.
Prior reports demonstrated that cells of the oligodendroglial lineage are susceptible to excitotoxic necrosis mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluR), and also showed that these cells express the high affinity neurotrophin receptors, TrkC and TrkA. We now report that: a) oligodendroglial progenitors (OP) and immature oligodendroglia are more vulnerable to AMPA-GluR-mediated excitotoxicity than are mature oligodendroglia; b) TrkC expression falls substantially during differentiation of cultured OP to mature oligodendroglia, whereas TrkA expression increases markedly; and c) neurotrophin-3, and to a lesser extent, nerve growth factor, protect the oligodendroglial lineage against AMPA-GluR-mediated excitotoxicity.
Kavanaugh
B
B
Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Beesley
J
J
Itoh
T
T
Itoh
A
A
Grinspan
J
J
Pleasure
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D004351:Drug Resistance; D007425:Intracellular Membranes / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D009498:Neurotoxins; D020933:Neurotrophin 3; D018091:Receptors, AMPA; D017475:Receptors, Nerve Growth Factor; D002118:Calcium