Evaluation of seizure foci and genes in the Lgi1(L385R/+) mutant rat

Neurosci Res. 2014 Mar;80:69-75. doi: 10.1016/j.neures.2013.12.008. Epub 2014 Jan 6.

Abstract

Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically relevant features of Lgi1 heterozygous mutant rats (Lgi1(L385R/+)) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1(L385R/+) and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1(L385R/+) rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1(L385R/+) rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1(L385R/+) rats are useful as an animal model of human ADLTE.

Keywords: ADLTE; EEG; Fos; LGI1; Microarray; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Electroencephalography
  • Epilepsy, Reflex / genetics*
  • Epilepsy, Reflex / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Intracellular Signaling Peptides and Proteins
  • Mice, Transgenic
  • Mutation, Missense / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Proteins / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Inbred F344

Substances

  • Intracellular Signaling Peptides and Proteins
  • Lgi1 protein, mouse
  • Proteins
  • Proto-Oncogene Proteins c-fos