Neurochemistry international
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Mesial temporal lobe epilepsy (MTLE) is the most prevalent form of epilepsy, characterized by recurrent complex partial seizures and hippocampal sclerosis. The pathophysiology underlying this disorder remains unidentified. While a loss of benzodiazepine binding sites is a key diagnostic feature of MTLE, experimental studies have shown enhanced inhibitory transmission and increased expression of GABA(A)-receptors, suggesting that compensatory mechanisms are operative in epileptic hippocampus. ⋯ This indicates that the regulation of GABA(A)-receptor expression is related to chronic recurrent seizures, and is not due to the extrahippocampal neuronal damage affecting pilocarpine-treated rats. These results allow causal relationships in the induction and maintenance of chronic recurrent seizures to be distinguished. The loss of a critical number of interneurons in the DG is a possible cause of seizure initiation, whereas the long-lasting upregulation of GABA(A)-receptors in granule cells represents a compensatory response to seizure activity.
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We examined the effects of cytidine (5?)-diphosphocholine (CDP-choline) on plasma levels of cytidine, choline, and unchanged CDP-choline among normal volunteers receiving the substance orally or intravenously, and rats receiving it intravenously. Two hours after a single oral dose (2g), plasma choline levels were increased by 48% and plasma cytidine by 136%. Among subjects receiving three doses (2g each) at two-hour intervals, plasma choline peaked (30% over baseline) 4 h after the initial CDP-choline dose, while plasma cytidine levels continued to increase for at lest 6 h, at which time they were five times basal levels (P < 0.01). ⋯ In rats given a bolus injection of CDP-choline, five minutes earlier, the unchanged compound was also undetectable in plasma, while plasma cytidine levels increased markedly and remained elevated for at least 60 min. These observations show that CDP-choline is converted to at least two major circulating metabolites, choline and cytidine. Since both of these compounds are used in the biosynthesis of phosphatidylcholine, both may be involved in the long-term effects of the CDP-choline.