Immediate Early Gene Expression in Experimental Epilepsy


Dr. M. Kiessling, Institute of Neuropathology, University of Heidelberg, D-69120 Heidelberg, Germany Tel. +49 (6221) 562 603; Fax +49 (6221) 563 466


Neuronal excitation by experimentally induced seizures elicits the rapid induction of a set of genes called immediate early genes (IEGs). The gene products of fos, jun and Krox, multimember gene families that belong to the class of IEGs, participate in a fundamental biological control mechanism, the regulation of gene transcription. IEG encoded proteins act as third messengers in an intracellular signal transduction cascade between neural cell surface receptors, cytoplasmic second messenger systems and specific target genes in the nucleus, a process for which the term ‘stimulus transcription coupling’ has been given. Almost all types of seizures cause dynamic alterations of IEG expression in neurons of the limbic system, but also in non-limbic areas, such as the cortex, striatum and thalamus. IEG encoded transcription factors are thought to up- or down-regulate effector genes with preferential expression in the central nervous system, including genes for neurotransmitters, growth factors, receptors, synaptic and axonal proteins. If the concept holds true that IEGs act as molecular switches converting epileptic short-term excitation of neurons into alterations of the molecular phenotype, future research may help to explain hitherto unexplained phenomena in epileptogenesis including changes of synaptic efficacy, kindling and sprouting.