Epileptogenesis: GABAA Receptor Subtypes in Human Temporal Lobe Epilepsy

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Partial epilepsy often results from a brain insult. The development of epilepsy in this situation is termed epileptogenesis. Describe the changes in GABA(A) receptor mediated transmission that occur with epileptogenesis in the hippocampus, and the implications that such changes have for the development of epilepsy. 2010 Epilepsy is a quite common disorder that about 0.5-1 in 100 people are affected. It could happen through entire life but have a higher incidence in young children and elderly. The onset of the seizure is normally spontaneous without an immediate cause. During the seizure the patients show an abnormal excessive neuronal activity in the brain. The reason of the epilepsy is complex, as both environmental and genetic factors could play a role individually or together. While the genetic mutation is more common in children, brain insult such as trauma, stroke could be the main reason for elder people. Despite various reasons, in most condition of epilepsy a region of neuron network is promoted with increase excitability such as increased glutamate release, upregulated NMDA receptors, and/or less inhibition. Generally the inhibition in the brain is mediated by GABA receptors, by hyperpolarizing the neurons via chloride channels. This essay will focus on the change of GABA receptors, especially fast ionic GABAARs, that occur with the epileptogenesis in the hippocampus and its implacations. Both animal and human experiments have demostrated that epileptogenesis is associated to the GABAARs subunit alteration. In rat models, by patch-clamping recording and single cell mRNA amplification of dentate granule cell, Brooks-Kayal et al (1998), have found the α4 unit of GABA receptors increased whilst the α1 unit decresed. The... ... middle of paper ... ...ecific GABA transporter antagonists synergistically modulate phasic and tonic GABA a conductances in rat neocortex. J. Neurophysiol. 94, 2073e2085. Semyanov, A., Walker, M.C., Kullmann, D.M., Silver, R.A., 2004. Tonically active GABA A receptors: modulating gain and maintaining the tone. TINS 27, 262e269. Maguire, J.L., Stell, B.M., Rafizadeh, M., Mody, I., 2005. Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat. Neurosci. 8, 797e804. Patrylo, P.R., Spencer, D.D., Williamson, A., Ortinski, P.I., Turner, J.R., Barberis, A., Motamedi, G., Yasuda, R.P., Wolfe, B., Kellar, K.J., Vicini, S., Mcnay, E.C., Mccrimmon, R.J., Sherwin, R.S., 2001. GABA uptake and heterotransport are impaired in the dentate gyrus of epileptic rats and humans with temporal lobe sclerosis. J. Neurophysiol. 85, 1533e1542.

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