title: Molecular pathways controlling inhibitory receptor expression.
abstract: Epilepsy is a disease of complex etiology, and multiple molecular mechanisms contribute to its development. Temporal lobe epilepsy (TLE) may result from an initial precipitating event such as hypoxia, head injury, or prolonged seizure (i.e., status epilepticus [SE]), that is followed by a latent period of months to years before spontaneous seizures occur. γ-Aminobutyric acid (GABA)(A)  receptor (GABA(A) R) subunit changes occur during this latent period and may persist following the onset of spontaneous seizures. Research into the molecular mechanisms regulating these changes and potential targets for intervention to reverse GABA(A) R subunit alterations have uncovered seizure-induced pathways that contribute to epileptogenesis. Several growth or transcription factors are known to be activated by SE, including (but not limited to): brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), inducible cAMP early repressor (ICER), and early growth response factors (Egrs). Results of multiple studies suggest that these factors transcriptionally regulate GABA(A) R subunit gene expression in a way that is pertinent to the development of epilepsy. This article focuses on these signaling elements and describes their possible roles in gene regulatory pathways that may be critical in the development of chronic epilepsy.
authors.affiliation: Translational Epilepsy Program, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Grabenstatter
authors.forename: Shelley J
authors.initials: SJ
authors.lastname: Russek
authors.forename: Amy R
authors.initials: AR
authors.lastname: Brooks-Kayal
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051765:Early Growth Response Transcription Factors / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009414:Nerve Growth Factors / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D051765:Early Growth Response Transcription Factors; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A