The possible role of GABAA receptors and gephyrin in epileptogenesis

The term epileptogenesis refers to a dynamic alteration in neuronal excitability that promotes the appearance of spontaneous seizures. Temporal lobe epilepsy (TLE), the most common type of acquired epilepsy, often develops after an insult to the brain such as trauma, febrile seizures, encephalitis, or status epilepticus (SE). During the pre-epileptic state (also referred as latent or silent period) there is a plethora of molecular, biochemical and structural changes that lead to the generation of recurrent spontaneous seizures (or epilepsy). The specific contribution of these alterations to epilepsy development is unclear, but a loss of inhibition has been associated with the increased excitability detected in the latent period. A rapid increase in neuronal hyperexcitability could be due, at least in part, to a decline in the number of physiologically active GABAA receptors (GABAAR). Altered expression of scaffolding proteins involved in the trafficking and anchoring of GABAAR could directly impact the stability of GABAergic synapses and promote a deficiency in inhibitory neurotransmission. Uncovering the molecular mechanisms operating during epileptogenesis and its possible impact on the regulation of GABAAR and scaffolding proteins may offer new targets to prevent the development of epilepsy.