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

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.
AuthorsShengming Yin, Zhuo Guan, Yiyuan Tang, Jie Zhao, Jaushyong Hong, Wanqin Zhang
JournalBrain research (Brain Res) Vol. 1053 Issue 1-2 Pg. 195-202 (Aug 16 2005) ISSN: 0006-8993 [Print] Netherlands
PMID16039622 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • Excitatory Amino Acid Agonists
  • Itmap1 protein, rat
  • Membrane Proteins
  • Tyrosine 3-Monooxygenase
  • Kainic Acid
  • Animals
  • Behavior, Animal
  • Carrier Proteins (genetics, metabolism)
  • Cell Count (methods)
  • Excitatory Amino Acid Agonists (toxicity)
  • Gene Expression Regulation (drug effects)
  • Immunohistochemistry (methods)
  • In Situ Hybridization (methods)
  • Kainic Acid (toxicity)
  • Male
  • Maze Learning (drug effects)
  • Membrane Proteins (genetics, metabolism)
  • Memory Disorders (chemically induced, genetics, physiopathology)
  • Rats
  • Rats, Sprague-Dawley
  • Spatial Behavior (drug effects)
  • Status Epilepticus (chemically induced, complications, genetics, metabolism)
  • Time Factors
  • Tyrosine 3-Monooxygenase (metabolism)
  • Ventral Tegmental Area (metabolism)

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