Abstract
In the present electrophysiological study the effect of aminooxyacetic acid (AOAA) on the cortical epileptogenicity, and on the basic electro-cortical activity was investigated in anesthetized rats.
AOAA did not induce spontaneous epileptiform discharges but modified the somato-sensory evoked responses and the cortical epileptogenicity (induced by 4-aminopyridine) in the same manner depending on its concentration. AOAA at low concentrations increased the amplitude of evoked responses and the ipsilateral manifestation of epileptiform activity, however, at high concentrations significantly suppressed both the evoked responses and the induction and expression of seizures discharges. The anti-convulsive effect of AOAA was time-dependent (reached its maximum after 2h AOAA pre-treatment) and reversible. AOAA at low concentrations probably increases the efficacy of the NMDA excitatory system and decreases GABA-synthesis, resulting neuronal hyperexcitation. However, AOAA at high concentrations can lead to an effective cortical inhibition through intra- and extracellular accumulation of GABA. The gradual GABA accumulation - up to a certain level - at the synapses could also explain the time-dependency of the anticonvulsive effect of AOAA.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Bruton, C. J. (1988) The neuropathology of temporal lobe epilepsy, Oxford University Press.
Buzsáki, Gy., Traub, R. D. (1997) Physiological basis of EEG activity. In: Engel, J. Jr., Pedley, T. A. (eds) Epilepsy: A comprehensive textbook. Lippincott-Raven Publishers, Philadelphia.
Collins, R. C., Mehta, S. (1978) Effect of aminooxyacetic acid (AOAA) on focal penicillin seizures. Brain Res. 157, 311–320.
DeVanzo, J. P., Matthews, R. J., Stafford, J. E. (1964) Studies on the mechanism of action of aminooxyacetic acid. I. Reversal of aminooxyacetic acid-induced convulsions by various agents. Tox. Appl. Pharmacol. 6, 388–395.
Du, F., Eid, T., Schwarcz, R. (1998) Neuronal damage after the injection of aminooxyacetic acid into the rat entorhinal cortex: A silver impregnation study. Neuroscienc. 82, 1165–1178.
Eid, T., Schwarcz, R., Ottersen, O. P. (1999) Ultrastructure and immunocytochemical distribution of GABA in layer III of the rat medial entorhinal cortex following aminooxyacetic acid-induced seizures. Exp. Brain Res. 125, 463–475.
Foster, A. C., Vezzani, A., French, E. D., Schwarcz, R. (1984) Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci. Lett. 48, 273–278.
Fukao, K., Momiyama, T., Ishihara, K., Ujihara, H., Fujita, Y., Taniyama, K., Serikawa, T., Sasa, M. (1998) Inhibition by gamma-aminobutyric acid system activation of epileptic seizures in spontaneously epileptic rats. Jpn. J. Pharmacol. 76, 387–396.
Gupta, A., Wang, Y., Markram, H. (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Scienc. 287, 273–278.
Hicks, T. P., Conti, F. (1996) Amino acids as the source of considerable excitation in cerebral cortex. Can. J. Physiol. Pharmacol. 74, 341–361.
Kozlowski, V. L. (1988) Experimental study of the antiepileptic activity of fenibut and its combinations with sodium valproate and aminooxyacetic acid. Farmakol. Toksikol. 51, 18–21.
Kuriyama, K., Roberts, E., Rubinstein, M. K. (1966) Elevation of gamma-aminobutyric acid in brain with amino-oxyacetic acid and susceptibility to convulsive seizures in mice: a quantitative re-evaluation. Biochem. Pharmacol. 15, 221–236.
Le Gal, S., La Salle, G. (1980) Inhibition of kindling-induced generalized seizures by aminooxyacetic acid. Can. J. Physiol. Pharmacol. 58, 7–11.
Löscher, W. (1986) Development of tolerance to the anticonvulsant effect of GABAmimetic drugs in genetically epilepsy-prone gerbils. Pharmacol. Biochem. Behav. 24, 1007–1013.
Löscher, W., Hörstermann, D. (1994) Differential effects of vigabatrin, gamma-acetylenic GABA, aminooxyacetic acid and valproate on levels of various amino acids in rat brain regions and plasma. Naunyn. Schmiedebergs. Arch. Pharmacol. 349, 270–278.
Löscher, W., Hönack, D., Gramer, M. (1989) The use of inhibitors of GABA-transaminase for the estimation of GABA turnover in various brain regions of rats: a re-evaluation of aminooxyacetic acid. J. Neurochem. 53, 1737–1750.
McMaster, O. G., Du, F., French, E. D., Schwartz, R. (1991) Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. Exp. Neurol. 113, 378–385.
Minatogawa, Y., Noguchi, T., Kido, R. (1974) Kynurenine pyruvate transaminase in rat brain. J. Neurochem. 23, 271–272.
Orrego, F., Miranda, R. (1976) Electrical induced release of (3H)GABA from neocortical thin slices. Effects of stimulus waveform and amino-oxyacetic acid. J. Neurochem. 26, 1033–1038.
Pin, J. P., Bockaert, J. (1989) Two distinct mechanisms, differentially affected by excitatory amino acids, trigger GABA release from fetal mouse striatal neurons in primary culture. J. Neurosci. 9, 648–656.
Scharfman, H. E., Goodman, J. H., Du, F., Schwarcz, R. (1998) Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss. J. Neurophysiol. 80, 3031–3046.
Snodgrass, S. R., Iverson, L. L. (1973) Effects of AOAA on (3H)GABA uptake by rat brain slices. J. Neurochem. 20, 431–439.
Speciale, C., Wu, H. Q., Gramsbergen, J. B., Turski, W. A., Ungerstedt, U., Schwarcz, R. (1990) Determination of extracellular kynurenic acid in the striatum of unanaesthetized rats: effect of aminooxyacetic acid. Neurosci. Lett. 14, 198–203.
Szente, M. B., Boda, B. (1994) Cellular mechanisms of neocortical secondary epileptogenesis. Brain Res. 648, 203–214.
Szente, M. B., Pongrácz, F. (1979) Aminopyridine-induced seizure activity. EEG Clin. Neurophysiol. 46, 605–608.
Thomson, J. L., Holmes, G. L., Taylor, G. W., Feldman, D. R. (1988) Effects of kynurenic acid on amygdaloid kindling in the rat. Epilepsy Res. 2, 302–308.
Turski, W. A., Dziki, M., Urbanska, E., Calderazzo-Filho, L. S., Cavalheiro, E. A. (1991) Seizures induced by aminooxyacetic acid in mice: Pharmacological characteristics. Synaps. 7, 173–180.
Turski, W. A., Dziki, M., Parada, J., Kleinrok, Z., Cavalheiro, E. A. (1992) Age dependency of the susceptibility of rats to aminooxyacetic acid seizures. Dev. Brain Res. 67, 137–144.
Urbanska, E., Ikonomidou, C., Sielucka, M., Turski, W. A. (1991) Aminooxyacetic acid produces excitotoxic leisons in rat striatum. Synaps. 9, 129–135.
Vécsei, L., Beal, F. M. (1992) Behavioural and pharmacological effects of centrally administrated aminooxyacetic acid in rats. Eur. J. Pharmacol. 220, 259–262.
Wood, J. D., Russell, M. P., Kurylo, E., Newstead, J. D. (1979) Stability of synaptosomal GABA levels and their use in determining the in vivo effects of drugs: convulsant agents. J. Neurochem. 33, 61–68.
Wood, J. D., Russell, M. P., Kurylo, E. (1980) The ψ-aminobutyrate content of nerve endings (synap-tosomes) in mice after the intramuscular injection of ψ-aminobutyrate-elevating agents: A possible role in anticonvulsant activity. J. Neurochem. 35, 125–130.
Wuarin, J. P., Dudek, F. E. (1996) Electrographic seizures and new recurrent excitatory circuits in the dentate gyrus of hippocampal slices from kainate-treated rats. J. Neurosci. 16, 4438–4448.
Zilberter, Y. (2000) Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurones in rat neocortex. J. Physiolog. 528, 489–496.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Barna, B., Szász, A., Asztalos, T. et al. Concentration- and Time-Dependent Effect of Aminooxyacetic Acid on Cortical Epileptogenicity. BIOLOGIA FUTURA 53, 245–256 (2002). https://doi.org/10.1556/ABiol.53.2002.3.1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/ABiol.53.2002.3.1