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Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

Translational Neuroscience volume 4, pages 429–436 (2013)Cite this article

Abstract

The anticonvulsants that are currently available modulate the activity of neuronal receptors and ion channels, which are equally involved in apoptotic pathways. We investigated the hypothesis that gabapentin (GP), an anticonvulsant without effect on glutamate receptors acting as GABA analog, has neuroprotective properties. For comparison, we chose topiramate (TPM), which has been reported to be neuroprotective via AMPA receptors blockade. For this purpose, we used rat cerebellar granule neuron (CGN) cultures and we triggered apoptosis independent of glutamate receptors with staurosporine, a broad-spectrum protein kinase inhibitor. GP at therapeutic range concentration significantly increased cell viability in CGN cultures maintained in physiological KCl concentration and reversed apoptosis induced by staurosporine. Blockade of NMDA or AMPA receptors by MK801 or NBQX, respectively, did not alter GP neuroprotection, which was reversed instead by GABA. In contrast, protective effect of TPM on STS-treated CGN cultures was annihilated by NBQX, and not altered by MK801 or GABA. Treatments with neuroprotective concentrations of GP or TPM did not modify the expression of neuronal cell adhesion molecule or synaptophysin or the morphological aspect of neuronal endings. In summary, we report that GP is neuroprotective through glutamate-receptor independent mechanisms and without alteration of neuronal plasticity markers, which makes it a possible candidate for clinical neuroprotection trials.

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Author information

Authors and Affiliations

  1. Department of Neuroscience and Molecular Medicine, ‘Victor Babeş’ National Institute for Research and Development in the Field of Pathology and Biomedical Sciences, Bucharest, Romania

    Bogdan O. Popescu

  2. Department of Neurology, Colentina Clinical Hospital — CDPC, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania

    Bogdan O. Popescu

  3. Centre d’études Avancées en Médecine du Sommeil, Hôpital du Sacré-Coeur de Montréal, and Department of Psychology, University of Montreal, Montreal, Quebec, Canada

    Maria Ţuineag

  4. Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London, London, SE5 8AF, UK

    Radu Stoica

Authors
  1. Bogdan O. Popescu
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  2. Maria Ţuineag
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  3. Radu Stoica
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Correspondence to Bogdan O. Popescu.

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Popescu, B.O., Ţuineag, M. & Stoica, R. Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons. Translat.Neurosci. 4, 429–436 (2013). https://doi.org/10.2478/s13380-013-0139-9

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  • DOI: https://doi.org/10.2478/s13380-013-0139-9

Keywords

  • Antiepileptic drugs
  • Gabapentin
  • Topiramate
  • Neuroprotection
  • Apoptosis
  • Neurodegeneration