Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.
Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.
Yi
Jung-Sun
JS
National Creative Research Initiative Center for the Study of CNS Zinc, University of Ulsan College of Medicine, 138-736 Seoul, South Korea.
Lee
Soon-Keum
SK
Sato
Taka-Aki
TA
Koh
Jae-Young
JY
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015032:Zinc / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C485843:Bex3 protein, rat; D002614:Chelating Agents; D011506:Proteins; D020800:Receptor, Nerve Growth Factor; D004492:Edetic Acid; D015032:Zinc; D007608:Kainic Acid