Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy

Aarne M A Ylinen, Riitta Miettinen, Asla Pitkänen, Attila I. Gulyas, T. Freund, Paavo J. Riekkinen

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of γ-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment. (.

Original languageEnglish
Pages (from-to)7650-7653
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number17
Publication statusPublished - 1991

Fingerprint

Epilepsy
gamma-Aminobutyric Acid
Cell Death
4-Aminobutyrate Transaminase
Perforant Pathway
Aminobutyrates
Afferent Pathways
Crows
Temporal Lobe Epilepsy
Neurobiology
Pyramidal Cells
Kainic Acid
Neurotoxins
Somatostatin
Synaptic Transmission
Cognition
Electric Stimulation
Hippocampus
Seizures
Placebos

Keywords

  • Excitotoxicity
  • Perforant pathway stimulation
  • Somatostatin
  • Vigabatrin

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. / Ylinen, Aarne M A; Miettinen, Riitta; Pitkänen, Asla; Gulyas, Attila I.; Freund, T.; Riekkinen, Paavo J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 17, 1991, p. 7650-7653.

Research output: Contribution to journalArticle

Ylinen, Aarne M A ; Miettinen, Riitta ; Pitkänen, Asla ; Gulyas, Attila I. ; Freund, T. ; Riekkinen, Paavo J. / Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 17. pp. 7650-7653.
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