Increased expression of cathepsin D in retrosplenial cortex of MK-801-treated rats.
Single administration of a high dose of an uncompetitive NMDA receptor antagonist-dizocilpine maleate (MK-801)-results in transient neuronal vacuolization and cell death in retrosplenial cortex in rodents. In this study expression of cathepsin D (CatD), a major lysosomal aspartic protease, was investigated in brains of female rats treated with 1, 5, or 10 mg/kg of MK-801. Northern blot analysis demonstrated that the CatD mRNA level was moderately increased in retrosplenial cortex 24 h-7 days after the treatment. Concomitantly, increased CatD immunoreactivity was observed, predominantly in the degenerating neurons in layer III of retrosplenial cortex. Neuronal response was spatially distinguished from glial reactivation marked by increased mRNA and protein levels of glial fibrillary acidic protein, as demonstrated by Northern blot and immunohistochemistry in retrosplenial cortex 24 h-7 days after MK-801 treatment. These data suggest that activation of the lysosomal proteolytic system of neurons may play a role in MK-801-evoked neurodegeneration.
Hetman
M
M
Nencki Institute of Experimental Biology, Warsaw, Poland.
Danysz
W
W
Kaczmarek
L
L
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002402:Cathepsin D / Q000096:biosynthesis* / Q000235:genetics; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D009410:Nerve Degeneration / Q000139:chemically induced*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D010296:Parietal Lobe / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D014617:Vacuoles / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002402:Cathepsin D