A sublethal dose of TNFalpha potentiates kainate-induced excitotoxicity in optic nerve oligodendrocytes.
Glutamate receptor-induced cell death, known as excitotoxicity in both neurons and oligodendrocytes, has been implicated as a common pathway of cell death in numerous central nervous system (CNS) diseases and trauma. Research in both neuronal and oligodendrocyte excitotoxicity has examined glutamate's receptor-mediated effects on CNS cells, and explored strategies to protect cells exposed to the elevated glutamate levels that occur in CNS trauma and disease. Proinflammatory cytokines are also elevated in the injured CNS, and have also been implicated in CNS cell death. Recently, several laboratories have examined cytokines' effects on neuronal and glial excitotoxicity. Here, we review literature concerning the dynamic susceptibility of both neurons and oligodendrocytes to excitotoxicity, and present new data from our laboratory showing that the susceptibility of oligodendrocytes to excitotoxicity is acutely potentiated by the proinflammatory cytokine TNFalpha.
Miller
Brandon A
BA
Department of Neuroscience, The Ohio State University, College of Medicine, 333 W. 10th Ave, Columbus, OH 43210, USA.
Sun
Fang
F
Christensen
Randolph N
RN
Ferguson
Adam R
AR
Bresnahan
Jacqueline C
JC
Beattie
Michael S
MS
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity*; D009836:Oligodendroglia / Q000187:drug effects*; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D014409:Tumor Necrosis Factor-alpha; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D007608:Kainic Acid