GABAergic Mechanisms in Epilepsy
Open accessAbstract
Summary: γ‐Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tone that counterbalances neuronal excitation. When this balance is perturbed, seizures may ensue. GABA is formed within GABAergic axon terminals and released into the synapse, where it acts at one of two types of receptor: GABA A , which controls chloride entry into the cell, and GABA B , which increases potassium conductance, decreases calcium entry, and inhibits the presynaptic release of other transmitters. GABA A ‐receptor binding influences the early portion of the GABA‐mediated inhibitory postsynaptic potential, whereas GABA B binding influences the late portion. GABA is rapidly removed by uptake into both glia and presynaptic nerve terminals and then catabolized by GABA transaminase. Experimental and clinical study evidence indicates that GABA has an important role in the mechanism and treatment of epilepsy: (a) Abnormalities of GABAergic function have been observed in genetic and acquired animal models of epilepsy; (b) Reductions of GABA‐mediated inhibition, activity of glutamate decarboxylase, binding to GABA A and benzodiazepine sites, GABA in cerebrospinal fluid and brain tissue, and GABA detected during microdialysis studies have been reported in studies of human epileptic brain tissue; (c) GABA agonists suppress seizures, and GABA antagonists produce seizures; (d) Drugs that inhibit GABA synthesis cause seizures; and (e) Benzodiazepines and barbiturates work by enhancing GABA‐mediated inhibition. Finally, drugs that increase synaptic GABA are potent anticonvulsants. Two recently developed antiepileptic drugs (AEDs), vigabatrin (VGB) and tiagabine (TGB), are examples of such agents. However, their mechanisms of action are quite different (VGB is an irreversible suicide inhibitor of GABA transaminase, whereas TGB blocks GABA reuptake into neurons and glia), which may account for observed differences in drug side‐effect profile.
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Substantial evidence shows that loss of GABAergic tone leads to seizures.
“Substantial evidence shows that loss of GABAergic tone leads to seizures [97].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [97]
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Cites
Which GABAA-receptor subtypes really occur in the brain?
McKernan, R. M., & Whiting, P. J. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80023-3 · Cited by 1,222 · see citing works
Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain
During, M. J., & Spencer, D. D. (1993) · The Lancet · doi:10.1016/0140-6736(93)90754-5 · Cited by 905 · see citing works
Houser, C. R., Miyashiro, J., Swartz, B. E., Walsh, G. O., Rich, J., & Delgado‐Escueta, A. V. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-01-00267.1990 · Cited by 619 · see citing works
Study, R. E., & Barker, J. L. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.7180 · Cited by 564 · see citing works
Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties.
Jenner, P. G. (1987) · Journal of Neurology Neurosurgery & Psychiatry · Cited by 371 · see citing works
IN-VIVO DEMONSTRATION OF REDUCED BENZODIAZEPINE RECEPTOR BINDING IN HUMAN EPILEPTIC FOCI
Savic, I., Roland, P. E., Sedvall, G., Persson, A., Pauli, S., & Widén, L. (1988) · The Lancet · doi:10.1016/s0140-6736(88)92468-3 · Cited by 364 · see citing works
Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus
Tl, B., Pretorius, J., Kupfer, W. R., & Crandall, P. H. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-07-02562.1989 · Cited by 363 · see citing works
Inhibitory, GABAergic Nerve Terminals Decrease at Sites of Focal Epilepsy
Ribak, C. E., Harris, A. B., Vaughn, J. E., & Roberts, E. (1979) · Science · doi:10.1126/science.109922 · Cited by 344 · see citing works
Hippocampal GABA transporter function in temporal-lobe epilepsy
During, M. J., Ryder, K. M., & Spencer, D. D. (1995) · Nature · doi:10.1038/376174a0 · Cited by 334 · see citing works
Suzdak, P. D., & Jansen, J. A. (1995) · Epilepsia · doi:10.1111/j.1528-1157.1995.tb02576.x · Cited by 278 · see citing works
Olsen, R. W., & Avoli, M. (1997) · Epilepsia · doi:10.1111/j.1528-1157.1997.tb01728.x · Cited by 260 · see citing works
USE AND ABUSE OF ELECTROENCEPHALOGRAPHY.
Lindahl‐Kiessling, K. (1964) · PubMed · Cited by 253 · see citing works
McDonald, J. W., Garofalo, E. A., Hood, T. W., Sackellares, J. C., Gilman, S., McKeever, P. E., Troncoso, J. C., & Johnston, M. V. (1991) · Annals of Neurology · doi:10.1002/ana.410290513 · Cited by 222 · see citing works
In vivo cerebral metabolism and central benzodiazepine‐receptor binding in temporal lobe epilepsy
Henry, T. R., Frey, K. A., Sackellares, J. C., et al. (1993) · Neurology · doi:10.1212/wnl.43.10.1998 · Cited by 190 · see citing works
Tiagabine for Complex Partial Seizures
Uthman, B. M., Rowan, A. J., Ahmann, P. A., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.1.56 · Cited by 146 · see citing works
Schwartz, R. D. (1988) · Biochemical Pharmacology · doi:10.1016/0006-2952(88)90684-3 · Cited by 138 · see citing works
French, J. A., Mosier, M. C., Walker, S., et al. (1996) · Neurology · doi:10.1212/wnl.46.1.54 · Cited by 134 · see citing works
“Central” and “peripheral” benzodiazepine receptors
Johnson, E. W., de Lanerolle, N. C., Kim, J. H., et al. (1992) · Neurology · doi:10.1212/wnl.42.4.811 · Cited by 119 · see citing works
Tiagabine Therapy for Complex Partial Seizures
Sachdeo, R. C. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550170069016 · Cited by 111 · see citing works
Baclofen has a proepileptic effect in the rat dentate gyrus.
Mott, D. D., Bragdon, A. C., Lewis, D. V., & Wilson, W. A. (1989) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23488-7 · Cited by 109 · see citing works
Neurotransmitters, Seizures, and Epilepsy III
Hammond, E. J., & Wilder, B. J. (1987) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-198704000-00009 · Cited by 107 · see citing works
Roberts, R. C., Ribak, C. E., & Oertel, W. H. (1985) · Brain Research · doi:10.1016/0006-8993(85)91303-4 · Cited by 99 · see citing works
Adjunctive treatment of partial seizures with tiagabine: A placebo-controlled trial
Richens, A., Chadwick, D. W., Duncan, J. S., et al. (1995) · Epilepsy Research · doi:10.1016/0920-1211(95)00006-v · Cited by 98 · see citing works
International Experience with Tiagabine Add‐On Therapy
Ben‐Menachem, E. (1995) · Epilepsia · doi:10.1111/j.1528-1157.1995.tb06010.x · Cited by 71 · see citing works
Olsen, R. W., Wamsley, J. K., McCabe, R. T., et al. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.19.6701 · Cited by 69 · see citing works
Houser, C. R., Harris, A. B., & Vaughn, J. E. (1986) · Brain Research · doi:10.1016/0006-8993(86)90014-4 · Cited by 65 · see citing works
Peterson, G. M., Ribak, C. E., & Oertel, W. H. (1985) · Brain Research · doi:10.1016/0006-8993(85)90937-0 · Cited by 64 · see citing works
Effects of vigabatrin on partial seizures and cognitive function.
Grünewald, R. A., Thompson, P. J., Corcoran, R., et al. (1994) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.9.1057 · Cited by 62 · see citing works
γ‐Aminobutyric Acid and Benzodiazepine Binding Sites in Audiogenic Seizure‐Susceptible Mice
Horton, R. W., Prestwich, S. A., & Meldrum, B. S. (1982) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1982.tb07972.x · Cited by 62 · see citing works
GABA/benzodiazepine receptors in human focal epilepsy
Olsen, R. W., Bureau, M., Houser, C. R., et al. (1992) · Elsevier eBooks · doi:10.1016/b978-0-444-89710-7.50053-7 · Cited by 58 · see citing works
Houser, C. R., Swartz, B. E., Walsh, G. O., & Delgado‐Escueta, A. V. (1992) · PubMed · Cited by 55 · see citing works
Swartzwelder, H. S., Bragdon, A. C., Sutch, C. P., et al. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24937-0 · Cited by 51 · see citing works
Recent advances in epilepsy. I
Volanschi, D. (1984) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(84)90144-5 · Cited by 42 · see citing works
Mechanisms of anticonvulsant drug action.
Macdonald, R. L., & McLean, M. J. (1987) · PubMed · Cited by 40 · see citing works
Changes in GABA-immunoreactive cell density during motor focal epilepsy induced by cobalt in the rat
Esclapez, M., & Trottier, S. (1989) · Experimental Brain Research · doi:10.1007/bf00247895 · Cited by 31 · see citing works
Beran, R. G., Berkovic, S. F., Buchanan, N., et al. (1996) · Seizure · doi:10.1016/s1059-1311(96)80018-5 · Cited by 30 · see citing works
Epilepsy and GABA Receptor Agonists Basic and Therapeutic Research
Meldrum, B. S. (1986) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.49.6.731 · Cited by 19 · see citing works
King, J. T., & LaMotte, C. C. (1988) · Brain Research · doi:10.1016/0006-8993(88)90218-1 · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Lloyd KG, Scatton B, Voltz C, et al. Amino acid and monoamine metabolite levels in CSF of Papio papio: correlation with photo- sensitive response. In: Nistico G, Morselli PL, Lloyd KG, et al., eds. Neurotransmitters, seizures, and epilepsy III. New York: Raven Press, 1986:151-62.
Cited by
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Unraveling mechanisms of homeostatic synaptic plasticity
Pozo, K., & Goda, Y. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.028 · Cited by 565 · see citing works
TREK-1, a K+ channel involved in neuroprotection and general anesthesia
Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang‐Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600234 · Cited by 534 · see citing works
Okaty, B. W., Miller, M. N., Sugino, K., Hempel, C. M., & Nelson, S. B. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0105-09.2009 · Cited by 309 · see citing works
Nimgampalle, M., Chakravarthy, H., Sharma, S., Shree, S., Bhat, A. R., Pradeepkiran, J. A., & Devanathan, V. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101994 · Cited by 207 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183 · see citing works
Characterizing and minimizing the contribution of sensory inputs to TMS-evoked potentials
Biabani, M., Fornito, A., Mutanen, T. P., Morrow, J., & Rogasch, N. C. (2019) · Brain Stimulation · doi:10.1016/j.brs.2019.07.009 · Cited by 158 · see citing works
Wang, D. D., & Kriegstein, A. R. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq124 · Cited by 148 · see citing works
Crandall, J. E., McCarthy, D. M., Araki, K. Y., Sims, J. R., Ren, J.-Q., & Bhide, P. G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5124-06.2007 · Cited by 134 · see citing works
NF-κB/Rel Regulates Inhibitory and Excitatory Neuronal Function and Synaptic Plasticity
O'Mahony, A., Raber, J., Montano, M., Foehr, E., Han, V., Lu, S.-M., Kwon, H., LeFevour, A., Chakraborty-Sett, S., & Greene, W. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00510-06 · Cited by 110 · see citing works
GABA release from astrocytes in health and disease.
Kilb, W., & Kirischuk, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415859 · Cited by 66 · see citing works
Hoffmann, E., Nomikos, G. G., Kaul, I., Raines, S., Wald, J., Bullock, A., Sankoh, A. J., Doherty, J., Kanes, S. J., & Colquhoun, H. (2020) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00801-0 · Cited by 59 · see citing works
Gabriel, J., Höfner, G., & Wanner, K. T. (2019) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00665 · Cited by 20 · see citing works
Gabriel, J., Höfner, G., & Wanner, K. T. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112598 · Cited by 3 · see citing works
- Authors
- Treiman, D. M.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Treiman, David M.
- ORCID
- Treiman, David M.
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2001-07
- Volume
- 42
- Issue
- s3
- Pages
- 8-12
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W2137976898
- Cited by
- 836
- References
- 38
- Citations by year
- 2026: 36 · 2025: 57 · 2024: 75 · 2023: 61 · 2022: 61 · 2021: 62 · 2020: 55 · 2019: 47 · 2018: 40 · 2017: 37 · 2016: 19 · 2015: 29 · 2014: 24 · 2013: 22 · 2012: 27
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- GABA, epilepsy, GABAA receptor, GABAB receptors, inhibitory neurotransmission, seizures, antiepileptic drugs, vigabatrin, tiagabine, GABA transaminase, GABA reuptake, benzodiazepines, barbiturates, glutamic acid decarboxylase, animal models of epilepsy
- MeSH terms
- 4-Aminobutyrate Transaminase, Animals, Disease Models, Animal, Epilepsy, gamma-Aminobutyric Acid, Humans, Models, Genetic, GABA Agonists, GABA Antagonists, Mice, Rats
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