Antivitamin B6 Induced Ultrastructural Changes in the Hippocampus of the Convulsant Rabbit and Its Biochemical Correlates
Although numerous attempts have been made to understand the mechanisms of epileptic seizure discharges (e.g. 7), no satisfactory explanation is available concerning a causative factor resulting in the onset of generalized seizure 14. One way of obtaining more information on this problem, is to study the supposed changes occurring just before the onset of the seizure, i. e. in the preictal period. For this purpose it is necessary to have a convulsant agent which acts with fairly constant time intervals, so that the moment at which the seizure starts can be predicted. This supposition is fulfilled by an antimetabolite of vitamin B6, methoxypyridoxine (MP). By competitively displacing pyridoxalphosphate from its binding sites at the apoenzymes of decarboxylases and transaminases 15, MP imitates a strong vitamin B6-deficiency, characterized by neuritis, ataxia, and spontaneous generalized convulsions 5. One of the most susceptible B6-enzymes is the glutamate decarboxylase 2, which controls the synthesis of the supposed inhibitory transmitter substance gammaaminobutyric acid (GABA). Already preictally the enzyme activity is markedly reduced (Nitsch, in preparation), so that consumed GABA cannot be replenished. The regional change of the GABA-concentration after administration of convulsive agents has not yet been systematically studied in spite of the fact, that GABA-levels differ among brain regions 13.
KeywordsPyramidal Cell Apical Dendrite Glutamate Decarboxylase Presynaptic Membrane Seizure Discharge
Unable to display preview. Download preview PDF.
- 5.Coursin, D. B. (1960), Seizures in vitamin Ba deficiency. In: Inhibition in the nervous system and GABA (Coursin, D. B, ed.), pp. 294–301. Pergamon Press.Google Scholar
- 6.Hassler, C., Hassler, R., Okada, Y., Bak, I. J. (1971), Pre-ictal and ictal changes of serotonin, GABA and glutamate contents in different regions of rabbit brain during methoxypyridoxine-induced seizures. Acta Neurol. Latinoam. 17, 595–611.Google Scholar
- 7.Jasper, H. H., Ward, A. A., Pope, A. (1969), Basic mechanisms of the epilepsies. Boston: Little, Brown and Co.Google Scholar
- 9.McKhann, G. M., Albers, R. W., Sokoloff, L., Mickelsen, O., Tower, D. B. (1960), The quantitative significance of the y-aminobutyric acid pathway in cerebral oxidative metabolism. In: Inhibition in the nervous system and GABA (McKhann, G. M., Albers, R. W., Sokoloff, L., Mickelsen, O., Tower, D. B, ed.), pp. 169–181. Pergamon Press.Google Scholar
- 12.Nitsch, C., Okada, Y. (1976), Differential decrease of GABA in the substantia nigra and other regions of the rabbit brain during methoxypyridoxine-induced convulsions. Brain Res. 105.Google Scholar
- 14.Prince, D. A. (1972), Topical convulsant drugs and metabolic antagonists. In: Experimental models of epilepsy ( Purpura, D. P., Penry, J. K., Tower, D., Woodbury, D. M., Walter, R., eds.), pp. 51–83. New York: Raven Press.Google Scholar
- 15.Purpura, D. P., Berl, S., Gonzales-Monteagudo, O., Wyatt, A. (1960), Brain amino acid changes during methoxypyridoxine-induced seizure (cat). In: Inhibition in the nervous system and GABA (Purpura, D. P., Berl, S., Gonzales-Monteagudo, O., Wyatt, A, ed.), pp. 331–335. Pergamon Press.Google Scholar
- 16.Purpura, D. P., Berl, S., Gonzales-Monteagudo, O., Wyatt, A., Gonzales-Monteagudo, O. (1960), Acute effects of methoxypyridoxine on hippocampal endblade neurons: an experimental study of “special pathoclisis” in the cerebral cortex. J. Neuropath. exp. Neurol. 19, 421–432.PubMedCrossRefGoogle Scholar