Abnormal serotonin receptor expression in DBA/2 mice associated with susceptibility to sudden death due to respiratory arrest

Victor V. Uteshev, Srinivasan Tupal, Yashanad Mhaskar, Carl L. Faingold

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Previous studies indicate that DBA/2 mice may be a useful model of human sudden unexpected death in epilepsy (SUDEP), since these mice exhibit generalized convulsive seizures followed by respiratory arrest (RA). Respiratory deficits, following generalized convulsive seizures, are observed prior to SUDEP in patients. RA that occurs in DBA/2 mice following sound-induced seizures can be prevented by treatments that activate serotonin (5-HT) receptors. 5-HT receptor subtypes in brainstem respiratory centers are important in regulating normal respiration. The present study compared the expression of 5-HT subtype receptor proteins in excised brainstem tissue, containing the rostral ventral medulla respiratory region in DBA/2 mice vs. seizure-resistant C57BL/6J mice, using Western blot analysis. The results indicate that expression of specific 5-HT2C, 5-HT3, and 5-HT4 receptor proteins in the brainstem tissue of DBA/2 mice is significantly diminished, while expression of the 5-HT2B receptors is significantly enhanced as compared to C57BL/6J mice. No difference in expression of 5-HT transporter protein is seen. These findings suggest that the DBA/2 mice are susceptible to RA, in part, because of the altered expression of 5-HT receptors. Preliminary studies indicate that 5-HT2C receptors may be particularly important, since a 5-HT2C agonist is very effective in blocking RA in DBA/2 mice.

Original languageEnglish
Pages (from-to)183-188
Number of pages6
JournalEpilepsy Research
Volume88
Issue number2-3
DOIs
StatePublished - 1 Feb 2010

Keywords

  • DBA/2 mice
  • Respiratory arrest
  • SUDEP
  • Serotonin receptors
  • Sudden unexplained death in epilepsy
  • Western blot

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