Abstract
The induction of the activity of cerebral ornithine decarboxylase (EC 4.1.1.17) and mRNA by electrical stimulation exhibits regional differences. The effects of the enzyme inhibitor difluoromethylornithine on these regional variations was examined. Administration of this inhibitor resulted in pronounced depression of both basal and induced activity of ornithine decarboxylase in the hippocampus. Basal activity of the enzyme in the neocortex and the cerebellum appeared to be resistant to difluoromethylornithine but the induced enzyme activity was sensitive to the effects of this inhibitor. Susceptibility to difluoromethylornithine may be directly correlated with a slower turnover rate for ornithine decarboxylase. These results suggest that ornithine decarboxylase in the hippocampus may possess a longer half-life than its counterparts in other regions of the brain. Pretreatment with difluoromethylornithine had no effect on the induced ornithine decarboxylase mRNA in the neocortex. Thus, elevated activity of ornithine decarboxylase enzyme, due to electrical stimulation, appears to not have any effect on either the transcription or the decay rate of the induced ornithine decarboxylase mRNA. These findings support the concept of region-specific regulation of cerebral ornithine decarboxylase.
Highlights
Unpublished observations from this laboratory indicated that the hippocampus exhibited the greatest elevation in enzyme activity, independent of direct changes in the levels of the ornithine decarboxylase messenger ribonucleic acid (mRNA)
Levels of the ornithine decarboxylase mRNA remained elevated for periods longer than 24 hr. This suggested a feedback inhibition of the rate of translation of the omithine decarboxylase mRNA. Unpublished observations from this laboratory indicated that the hippocampus exhibited the greatest elevation in enzyme activity, independent of direct changes in the levels of the ornithine decarboxylase mRNA
Assaying for activity of ornithine decarboxylase in different regions of the brain revealed a higher level of activity in the hippocampus and the lowest activity in the cerebellum (Fig. 1)
Summary
A single dose of this concentration has been shown to result in optimal inhibition of the activity of ornithine decarboxylase in tissues of the rat, within 4-6 hours (Danzin, Jung, Grove and Bey, 1979). To achieve maximum attenuation of activity of ornithine decarboxylase prior to electroshock, the solutions of difluoromethylornithine were administered in two doses, separated by 5 hours. Shock was applied at the following intensities: 85 mA for 1 sec with 1-msec pulses at a frequency of 50 Hz. Control animals were treated without the application of a current. Control animals were treated without the application of a current These intensities of shock have been demonstrated to be without detectable morphological damage to the brain (Dam, 1982).
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