Abnormal expression of epilepsy-related gene ERG1/NSF in the spontaneous recurrent seizure rats with spatial learning memory deficits induced by kainic acid

Shengming Yin, Zhuo Guan, Yiyuan Tang, Jie Zhao, Jaushyong Hong, Wanqin Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Previous epilepsy-related gene screen identified a spontaneous recurrent seizure (SRS)-related gene named epilepsy-related gene (ERG1) that encodes N-ethylmaleimide-sensitive fusion protein (NSF). To explore whether spatial learning memory deficits are relevant to SRS and whether hippocampal NSF expression is altered by SRS, we used the kainic acid (KA)-induced epilepsy animal model. SRS was monitored for 3 weeks after injection of a single convulsive dose of KA. KA-treated rats with SRS, KA-treated rats without SRS, and saline-treated rats were then measured in Morris water maze. In this spatial learning task, KA-treated rats with SRS performed poorer compared to those without SRS and those treated with saline. During the subsequent probe trials, KA-treated rats with SRS spent less swim path and time in the target quadrant but more swim path and time in the opposite quadrant, and showed fewer platform crossings. Moreover, in situ hybridization and immunohistochemistry showed that both ERG1/NSF mRNA and NSF immunoreactive expression were down-regulated in the CA1 and dorsal dentate gyrus cells (dDGCs) of the hippocampus, and interestingly, tyrosine hydroxylase (TH) immunoreactive dopamine (DA) neurons were lost in ventral tegmental area (VTA) in the KA rats with SRS. These data demonstrate that SRS impairs spatial learning memory and suggest that the down-regulation of NSF expression pattern in the hippocampus and the loss of DA neurons in VTA might contribute to the spatial learning memory deficits induced by SRS.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalBrain Research
Volume1053
Issue number1-2
DOIs
StatePublished - Aug 16 2005

Keywords

  • Epilepsy-related gene
  • Kainic acid
  • N-ethylmaleimide- sensitive fusion protein
  • Spatial learning memory
  • Spontaneous recurrent seizure
  • Ventral tegmental area

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