Kainic acid-induced naip expression in the hippocampus is blocked in mice lacking TNF receptors.
Mice that lack tumor necrosis factor-alpha (TNF) receptors are more susceptible than wild-type animals to brain injury produced by kainic acid or transient focal ischemia suggesting that the rapid production of TNF that occurs after these insults serves a neuroprotective role. The mechanisms by which TNF reduces neuronal loss after brain injury may involve the up-regulation of proteins that maintain calcium homeostasis or reduce free radical generation. We report here that systemic administration of kainic acid rapidly elevates expression of mRNA encoding neuronal apoptosis inhibitor protein (NAIP) in the hippocampus and that this increase does not occur in mice that lack TNF receptors. Given that NAIP overexpression can reduce neuronal injury by blocking apoptosis, our findings suggest that induction of the naip gene may contribute to the neuroprotective properties of TNF.
Thompson
Charles
C
Ottawa Hospital Research Institute, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Gary
Devin
D
Mattson
Mark
M
Mackenzie
Alex
A
Robertson
George S
GS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D007608:Kainic Acid; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D018696:Neuroprotective Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C496801:Naip1 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007608:Kainic Acid