Induction of ornithine decarboxylase mRNA in cerebral cortex in response to kainate lesion of nucleus basalis: involvement of NMDA receptors.
Excitotoxin lesion of nucleus basalis with kainate or ibotenate results in degeneration of cholinergic neurones and a subsequent cholinergic deficit in cerebral cortex ipsilateral to the lesion. This lesion is accompanied by a massive increase in ornithine decarboxylase (ODC) activity in ipsilateral cortex, which was further investigated in this study by assay of levels of ODC mRNA in cerebral cortex after lesion. Injection of kainate into the nucleus basalis induced a significant increase in ODC mRNA in ipsilateral cerebral cortex which was maximal at 8 h after lesion and declined to control levels by 72 h. This induction showed clear regional specificity and was completely prevented by injection of an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, at a dose of 1 mg/kg, 2 h after excitotoxin lesion. This study indicates that excitotoxin lesion causes an early and transient increase in ODC mRNA that is mediated by NMDA receptors and may represent a physiological response to injury.
Wood
H
H
Department of Biochemistry, Charing Cross and Westminster Medical School, London, U.K.
de Belleroche
J
J
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D004247:DNA; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009693:Nucleic Acid Hybridization; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*
D003986:Dibenzocycloheptenes; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D004247:DNA; D009955:Ornithine Decarboxylase