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

Neuroscience. 2001;106(1):79-88. doi: 10.1016/s0306-4522(01)00198-1.

Abstract

In various chemoconvulsant models of human temporal lobe epilepsy, the induction of epileptogenesis by a prolonged period of continuous seizure activity is accompanied by significant changes in hippocampal structure. These changes include an increase in neurogenesis within the proliferative subgranular zone (SGZ) of the dentate gyrus and induction of mossy fiber sprouting in mature dentate granule cells. As dentate granule cell neurogenesis and axon outgrowth are also hallmarks of hippocampal development, we hypothesized that molecules involved in normal development may also play a role in similar changes associated with epileptogenesis. To begin to test this hypothesis, we have analyzed the expression patterns of multiple members of the basic helix-loop-helix (bHLH) family of transcription factors in both normal and epileptic adult rats. bHLH protein expression has been found recently in 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 members examined in this study, as well as the divergent homeobox protein Prox1, is present in the adult. Patterns of expression varied considerably between family members, ranging from the limited expression of Mash1 in the neurogenic SGZ of the dentate gyrus to the scattered, widespread profile of Hes5 throughout the dentate gyrus and the hippocampus proper. Moreover, these varied profiles of expression were differentially regulated following status epilepticus, with some increasing (Mash1, Id2), some falling (Hes5, Prox1), 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 characterized, our findings support the idea that molecules controlling cell-fate decisions in the developing dentate gyrus are also operative during seizure-induced neurogenesis and plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Annexins / genetics
  • Basic Helix-Loop-Helix Transcription Factors
  • Bromodeoxyuridine / pharmacokinetics
  • Caenorhabditis elegans Proteins*
  • DNA-Binding Proteins / genetics
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / pathology
  • Dentate Gyrus / physiopathology
  • Epilepsy, Temporal Lobe / genetics*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / physiopathology
  • Gene Expression Regulation / physiology*
  • Helix-Loop-Helix Motifs / physiology*
  • Helminth Proteins / genetics
  • Homeodomain Proteins / genetics
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Male
  • Muscarinic Agonists / pharmacology
  • Neoplasm Proteins*
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity / physiology
  • Neuropeptides / genetics
  • Pilocarpine / pharmacology
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / genetics
  • Status Epilepticus / genetics*
  • Status Epilepticus / metabolism
  • Status Epilepticus / physiopathology
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins

Substances

  • Annexins
  • Ascl1 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Helminth Proteins
  • Hes5 protein, mouse
  • Hes5 protein, rat
  • Homeodomain Proteins
  • Id2 protein, rat
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Muscarinic Agonists
  • NEUROD2 protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Neurod2 protein, rat
  • Neuropeptides
  • Nex-1 protein, C elegans
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • Pilocarpine
  • ID3 protein, human
  • HES5 protein, human
  • NeuroD protein
  • Bromodeoxyuridine