Previous work in the applicants' laboratories demonstrated that seizures produced by focal lesions elicit a dramatic increase in enkephalin content and a concurrent decrease in dynorphon and cholecystokinin content in the hippocampal mossy fiber system of the adult rat and mouse. Additional work revealed that these effects are preceded by an increased transcription of mRNA for preproenkephalin, increased synthesis of enkephalin, and a massive but transient increase in ornithine decarboxylase (ODC) activity. Since ODC activity and polyamines have been linked to a variety of trophic responses in several types of cells, it was hypothesized that ODC induction and increased polyamine levels are responsible for the increased synthesis of enkephalin found after seizures. The proposed experiments will directly test this idea, identify the ananomical locus and biochemical nature of the ODC effect, and investigate the nature of the physiological events which trigger it. The specific goals of the proposed studies are as follows: 1) identify the hippocampal cells in which increased ODC activity occurs; 2) determine if physiological stimulation other than seizures can be used to induce ODC activity; 3) measure the effects of ODC Inhibition (and reduced polyamine levels) on seizure-induced changes in neuropeptides; 4) test the assumption that increased ODC activity is due to induction of the enzyme; and 5) examine the feasibility of using in vitro slices of hippocampus for further studies of ODC induction. Together these experiments will elucidate the process through which seizures, and possibly other physiological events, increase the activity of a potent trophic system (ODC) and test if this is responsible for alterations in the genomic machinery controlling neuropeptide levels.
| Arai, A; Baudry, M; Staubli, U et al. (1990) Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo. Brain Res Mol Brain Res 7:167-9 |
| Baudry, M; Shahi, K; Gall, C (1988) Induction of ornithine decarboxylase in adult rat hippocampal slices. Brain Res 464:313-8 |
