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Antivitamin B6 Induced Ultrastructural Changes in the Hippocampus of the Convulsant Rabbit and Its Biochemical Correlates

  • Cordula Nitsch
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 23)

Abstract

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.

Keywords

Pyramidal Cell Apical Dendrite Glutamate Decarboxylase Presynaptic Membrane Seizure Discharge 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Andersen, P., Eccles, J. C., Loyning, Y. (1964), Location of postsynaptic inhibitory synapses on hippocampal pyramids. J. Neurophysiol. 27, 592–607.PubMedGoogle Scholar
  2. 2.
    Bayoumi, R. A., Smith, W. R. D. (1973), Regional distribution of glutamic acid decarboxylase in the developing brain of the pyridoxine-deficient rat. J. Neurochem. 21, 603–613.PubMedCrossRefGoogle Scholar
  3. 3.
    Blackstad, T. W., Kjaerheim, A. (1961), Special axo-dendritic synapses in the hippocampal cortex. Electron and light microscopic studies on the layer of mossy fibres. J. Comp. Neurol. 117, 133–159.PubMedCrossRefGoogle Scholar
  4. 4.
    Ceccarelli, B., Hurlbut, W. P., Mauro, A. (1972), Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J. Cell Biol. 54, 30–38.PubMedCrossRefGoogle Scholar
  5. 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. 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. 7.
    Jasper, H. H., Ward, A. A., Pope, A. (1969), Basic mechanisms of the epilepsies. Boston: Little, Brown and Co.Google Scholar
  8. 8.
    Kim, J. S., Bak, I. J., Hassler, R., Okada, Y., (1971), Role of y-aminobutyric acid (GABA) in the extrapyramidal motor system. 2. Some evidence for the existence of a type of GABA-rich strio-nigral neurons. Exp. Brain Res. 14, 95–104.PubMedCrossRefGoogle Scholar
  9. 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
  10. 10.
    Moor, H., Mühlethaler, K. (1963), Fine structure in frozen-etched yeast cells. J. Cell Biol. 17, 609–628.PubMedCrossRefGoogle Scholar
  11. 11.
    Nitsch, C., Bak, I. J. (1974), Die Moosfaserendigungen des Ammonshorns, dargestellt in der Gefrierätztechnik. Verh. Anat. Ges. 68, 319–323.PubMedGoogle Scholar
  12. 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
  13. 13.
    Okada, Y., Nitsch-Hassler, C., Kim, J. S., Bak, I. J., Hassler, R. (1971), Role of y-aminobutyric acid (GABA) in the extrapyramidal motor system. 1. Regional distribution of GABA in rabbit, rat, guinea pig, and baboon CNS. Exp. Brain Res. 13, 514–518.PubMedCrossRefGoogle Scholar
  14. 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. 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. 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
  17. 17.
    Sotelo, C., Palay, S. (1968), The fine structure of the lateral vestibular nucleus in the rat. I. Neurons and neuroglial cells. J. Cell Biol. 36, 151–179.CrossRefGoogle Scholar
  18. 18.
    Storm-Mathisen, J. (1972), Glutamate decarboxylase in the rat hippocampal region after lesions of the afferent fibre systems. Evidence that the enzyme is localized in intrinsic neurons. Brain Res. 40, 215–235.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • Cordula Nitsch
    • 1
  1. 1.Neurobiologische AbteilungMax-Planck-Institut für HirnforschungFrankfurt/MainFederal Republic of Germany

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