Altered GABA A receptor expression during epileptogenesis

• Published in: Neuroscience letters Vol. 497; no. 3; pp. 218 - 222
• Main Authors: González, Marco I., Brooks-Kayal, Amy
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 27.06.2011
• Subjects: Animals; Brain - metabolism; Epilepsy; Epilepsy - physiopathology; Epileptogenesis; GABA receptors; Gene Expression Regulation; Humans; Nerve Tissue Proteins - metabolism; Receptor expression; Receptors, GABA-A - metabolism; Tissue Distribution; Transcriptional regulation; Epileptogenesis; Transcriptional regulation; GABA receptors; Epilepsy; Receptor expression
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.02.052

► GABA(A) receptor alterations precede spontaneous seizures and persist during epilepsy. ► An interplay among several signaling pathways regulates GABA(A) receptor expression. ► The JAK/STAT, CREB/ICER and Egr3 signaling pathways are activated by seizures. ► Transcriptional events triggered by SE may be critical for epilepsy development. ► A molecular understanding of epileptogenesis is essential to prevent or cure epilepsy. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA A receptors are heteropentamers formed by assembly of multiple subunits that generate a wide array of receptors with particular distribution and pharmacological profiles. Malfunction of these receptors has been associated with the pathophysiology of epilepsy and contribute to an imbalance of excitatory and inhibitory neurotransmission. The process of epilepsy development (epileptogenesis) is associated with changes in the expression and function of a large number of gene products. One of the major challenges is to effectively determine which changes directly contribute to epilepsy development versus those that are compensatory or not involved in the pathology. Substantial evidence suggests that changes in the expression and function of GABA A receptors are involved in the pathogenesis of epilepsy. Identification of the mechanisms involved in GABA A receptor malfunction during epileptogenesis and the ability to reverse this malfunction are crucial steps towards definitively answering this question and developing specific and effective therapies.