Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology

G. M. McKhann, H. J. Wenzel, C. A. Robbins, A. A. Sosunov, Philip A Schwartzkroin

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Genetic influences contribute to susceptibility to seizures and to excitotoxic injury, but it is unclear if/how these susceptibilities are linked. This study assessed the impact of genetic background on mouse strain seizure susceptibility, seizure phenotype, mortality, and hippocampal histopathology. A subcutaneous (s.c.) kainic acid multiple injection protocol was developed. Five mouse strains were tested: a and b) C57BL/6J and 129/SvJ, strains commonly used in gene targeting experiments; c) C3HeB/FeJ, a strain with reported sensitivity to the convulsant effects of kainic acid (KA); d) 129/SvEms, a strain reportedly susceptible to hippocampal excitotoxic cell death; and e) a mixed genetic background strain (129/SvJXC57BL/6J) from which targeted gene deletion experiments have been carried out. Histopathological features were examined at early (7-10 day), delayed (2-4 month), and late (6-13 month) time points. Mouse background strains can be genetically segregated based on excitotoxin sensitivity, seizure phenotype, mortality, and hippocampal histopathology. When injected with KA, C3HeB/FeJ and C57BL/6J strains were resistant to cell death and synaptic reorganization despite severe behavioral seizures, while 129/SvEms mice developed marked pyramidal cell loss and mossy fiber sprouting despite limited seizure activity. The mixed background 129/SvJXC57BL/6J group exhibited features of both parental strains. In the mouse strains tested, the duration or severity of seizure activity was not predictive of subsequent hippocampal pyramidal cell death and/or synaptic reorganization. Unlike rats, mice exhibiting prolonged high-grade KA-induced seizure activity did not develop subsequent spontaneous behavioral seizures.

Original languageEnglish (US)
Pages (from-to)551-561
Number of pages11
JournalNeuroscience
Volume122
Issue number2
DOIs
StatePublished - 2003

Keywords

  • Cell death
  • Excitotoxin
  • Mouse background strain
  • Variability

ASJC Scopus subject areas

  • Neuroscience(all)

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