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

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

Author information

1
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address: tmashimo@anim.med.kyoto-u.ac.jp.
3
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
4
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
5
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
6
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

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

PMID:
24406746
DOI:
10.1016/j.neures.2013.12.008
[Indexed for MEDLINE]

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