Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis.
Emerging data indicate that neurotrophic factors and cytokines utilize similar signal transduction mechanisms. Although neurotrophic factors can protect CNS neurons against a variety of insults, the role of cytokines in the injury response is unclear. We now report that TNF beta and TNF alpha (1-100 ng/ml) can protect cultured embryonic rat hippocampal, septal, and cortical neurons against glucose deprivation-induced injury and excitatory amino acid toxicity. The elevation of intracellular calcium concentration ([Ca2+]i) induced by glucose deprivation, glutamate, NMDA, or AMPA was attenuated in neurons pretreated with TNF beta. The mechanism whereby TNFs stabilize [Ca2+]i may involve regulation of the expression of proteins involved in maintaining [Ca2+]i homeostasis, since both TNF beta and TNF alpha caused a 4- to 8-fold increase in the number of neurons expressing the calcium-binding protein calbindin-D28k. These data suggest a neuroprotective role for TNFs in the brain's response to injury.
Cheng
B
B
Sanders-Brown Research Center on Aging, Lexington, Kentucky.
Christakos
S
S
Mattson
M P
MP
D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D006624:Hippocampus / Q000502:physiology; D006706:Homeostasis; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D005971:Glutamates; D008233:Lymphotoxin-alpha; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium