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Abnormalities of GABA System and Human Pharmacoresistant Epilepsy

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Pharmacoresistance in Epilepsy

Abstract

Despite the availability of various newly developed antiepileptic drugs (AEDs), pharmacoresistance remains a major challenge in epilepsy management. Unraveling the mechanisms underlying AED resistance has been the focus of intense efforts, in order to develop new rationally designed therapies for as yet refractory epilepsies. Based on experimental and clinical studies, one of the major neurobiological theories that has been put forward is the target hypothesis, which suggests that AEDs are not effective because of target alterations in the epileptogenic brain. Several studies have shown that seizure activity results in altered expression of gamma-aminobutyric acid (GABA) components such as GABA transporters (GATs) and GABA receptors. Indeed, changes in the composition of subunits expression appear to affect the functioning of GABAergic neurotransmission. Here, we review the current literature on epilepsy-associated changes in the GABA system conducted in experimental models and observations made in patients with treatment-resistant epilepsy, as well as genetic abnormalities in the GABA system in refractory human epilepsy.

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Acknowledgments

This study was supported by the Research in Health Found, FIS/IMSS/PROT/548 grant and National Council for Sciences and Technology of Mexico (Grant 98386). We thank Dr. Erika Brust-Mascher for English improvement.

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Authors and Affiliations

  1. Medical Research Unit in Neurological Diseases, National Medical Center, “Siglo XXI”, IMSS Hospital of Specialities, Cuauhtemoc No. 330-4, Col. Doctores, Mexico City, Mexico DF, 06720, Mexico

    Sandra Orozco-Suárez Ph.D., David Escalante-Santiago M.Sc. & Iris Angélica Feria-Romero Ph.D.

  2. Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Km. 15.5 Caretera Guadalajara-Nogales, Predio Las Agujas, Zapopan, Jalisco, 45110, Mexico

    Monica E. Ureña-Guerrero Ph.D.

  3. Department of Pharmacobiology, Center for Research and Advanced Studies, Bolivar 782-305, Col. Alamos, Del. Benito Juarez, Mexico City, 03400, Mexico

    Luisa Rocha M.D., Ph.D.

  4. ABC Hospital, Santa Fé, Neurology Center, and National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico

    Mario A. Alonso-Vanegas M.D.

  5. Pathology Department, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico

    Juana Villeda-Hernandez Ph.D.

  6. Department of Neurology and Neurosurgery, General Hospital of Mexico, Mexico City, Mexico

    Ana Luisa Velasco M.D., Ph.D.

Authors
  1. Sandra Orozco-Suárez Ph.D.
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  2. David Escalante-Santiago M.Sc.
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  3. Iris Angélica Feria-Romero Ph.D.
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  4. Monica E. Ureña-Guerrero Ph.D.
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  5. Luisa Rocha M.D., Ph.D.
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  6. Mario A. Alonso-Vanegas M.D.
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  7. Juana Villeda-Hernandez Ph.D.
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  8. Ana Luisa Velasco M.D., Ph.D.
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Corresponding author

Correspondence to Sandra Orozco-Suárez Ph.D. .

Editor information

Editors and Affiliations

  1. , Pharmacobiology Department, Center for Research and Advanced Studies, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico

    Luisa Rocha

  2. , Disciplina de Neurologia Experimental, UNIFESP/EPM, Rua Botucatu 740, São Paulo, 04023-900, Brazil

    Esper A. Cavalheiro

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Orozco-Suárez, S. et al. (2013). Abnormalities of GABA System and Human Pharmacoresistant Epilepsy. In: Rocha, L., Cavalheiro, E. (eds) Pharmacoresistance in Epilepsy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6464-8_9

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