Induction of ornithine decarboxylase in cerebral cortex by excitotoxin lesion of nucleus basalis: association with postsynaptic responsiveness and N-methyl-D-aspartate receptor activation.
The major cholinergic innervation of the rat cerebral cortex arises from the nucleus basalis in the basal forebrain. Introduction of the excitotoxins kainate or ibotenate into the nucleus basalis by stereotaxic injection results in degeneration of the cholinergic cells. We have investigated the effect of this excitotoxic action on ornithine decarboxylase (ODC) activity and cholinergic responsiveness in the cerebral cortex. A massive and rapid induction of ODC activity was seen in ipsilateral cortex after injection of excitotoxin. A maximal increase in ODC activity of 268 times the control value was seen in ipsilateral cerebral cortex 8 h after lesioning. Thereafter, ODC activity declined but remained significantly greater than control levels for 32 h. Pretreatment of animals with the irreversible ODC inhibitor difluoromethylornithine prevented the induction of ODC by kainate. Tissue content of the ODC product putrescine showed a marked increase in cerebral cortex ipsilateral to the lesion, increasing sevenfold at 24 h, the maximal concentration reached. After 24 h, the level of putrescine decreased but remained significantly elevated above control values for 5 days. Levels of the polyamines spermidine and spermine were unaffected by lesioning. Increases on ODC activity of much smaller magnitude were also seen in brain regions not directly innervated from the ipsilateral nucleus basalis. However, the response in ipsilateral cortex was found to be dependent on an intact projection from nucleus basalis to cortex. The induction of ODC was shown to be prevented by treatment of rats with MK-801, a result indicating the involvement of N-methyl-D-aspartate (NMDA) receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Reed
L J
LJ
Department of Biochemistry, Charing Cross and Westminster Medical School, London, England.
de Belleroche
J
J
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects*; D002540:Cerebral Cortex / Q000201:enzymology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D065108:Ornithine Decarboxylase Inhibitors; D010080:Oxazoles / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D013377:Substantia Innominata / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000502:physiology
D003986:Dibenzocycloheptenes; D018691:Excitatory Amino Acid Antagonists; D065108:Ornithine Decarboxylase Inhibitors; D010080:Oxazoles; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D013096:Spermine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009955:Ornithine Decarboxylase; D010424:Pentobarbital; D007608:Kainic Acid; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine