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 subunit alteration occurred after induction of status epilepsy by pilocarpine, and was preceded to the onset of spontaneous seizure. Apart from the morphological change, the pharmacology of the GABAR changed as well. Both efficacy and sensitivity of GABAR boost after epilepsy.
In human model (Loup et al., 2000), GABAAR subunits containing α1, α2, α3, β2, β3, and γ2are stained by immunohistochemistry. Although some other subunits are not studied, these subunits consist of 80% of all GABAAR. While the β2, β3, and γ2 present in most receptors, the α-subunits determine the distribution and pharmacological properties. Consisting with the animal model, the loss of α1 subunit was observed on most region of hippocampus, while an upregulation of α2 subunits occurred on the soma and apical dendrite.
Even though, the alteration of GABA receptor structure is proved to associate with epileptogenesis. It is still unclear, and hard to prove whether the receptor plasticity is a compensatory effect of the other epileptogenesis factors, or the change itself induce the epilepsy.
The dysfunction of synaptic GABAergic signaling contributes to epileptogenesis and generation of seizure. Generally, there are vast number of GABAergic...