Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus

In various chemoconvulsant models of human temporal lobe epilepsy, the indu ction of epiteptogenesis by a prolonged period of continuous seizure activi ty is accompanied by significant changes in hippocampal structure. These ch anges include an increase in neurogenesis within the proliferative subgranu lar zone (SGZ) of the dentate gyrus and induction of mossy fiber sprouting in mature dentate granule cells. As dentate granule cell neurogenesis and a xon outgrowth are also hallmarks of hippocampal development, we hypothesize d that molecules involved in normal development may also play a role in sim ilar changes associated with epileptogenesis. To begin to test this hypothe sis, we have analyzed the expression patterns of multiple members of the ba sic helix-loop-helix (bHLH) family of transcription factors in both normal and epileptic adult rats. bHLH protein expression has been found recently i n dentate, granule cells at specific developmental stages, and analysis of developmental models suggests specific neural differentiation functions for these molecules. We show that mRNA expression of all seven bHLH family mem bers examined in this study, as well as the divergent homeobox protein Prox 1, is present in the adult. Patterns of expression varied considerably betw een family members, ranging from the limited expression of Mash1 in the neu rogenic SGZ of the dentate, gyrus to the scattered, widespread profile of H es5 throughout the dentate gyrus and the hippocampus proper. Moreover, thes e varied profiles of expression were differentially regulated following sta tus epilepticus, with some increasing (Mash1, Id2), some falling (Hes5, Pro x1), and others remaining mostly unchanged (NeuroD/BETA2, NeuroD2/NDRF, Id3 , Rath2/Nex1). While the function of these molecules in the adult brain remains to be char acterized, our findings support the idea that molecules controlling cell-fa te decisions in the developing dentate gyrus are also operative during seiz ure-induced neurogenesis and plasticity. (C) 2001 IBRO. Published by Elsevi er Science Ltd. All rights reserved.