Developmental patterns in the regulation of chloride homeostasis and GABAA receptor signaling by seizures

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

GABAA receptors have dual functions during development. They depolarize immature neurons but hyperpolarize more mature neurons. This functional switch has been attributed to age-related differences in the relative abundance of cation chloride cotransporters, such as KCC2 and NKCC1, which regulate chloride homeostasis. Certain insults, such as trauma, ischemia, and seizures, if they occur when GABAAergic signaling is hyperpolarizing, such as in the adult brain, can lead to reappearance of the immature, depolarizing synaptic responses to GABAA receptor activation. In certain cases, this has been associated with either reduced expression of KCC2 or increase in NKCC1. In epilepsy, the depolarizing effects of GABAA receptors have been proposed to be important for the acquisition and/or maintenance of the epileptic state. Using the kainic acid model of status epilepticus, we have studied the effects of repetitive neonatal episodes of status epilepticus on the expression of cation chloride cotransporter KCC2 in the neonatal hippocampus. In contrast to adults, seizures increased KCC2 mRNA expression in the CA3 region of the neonatal hippocampus. The contrasting patterns of regulation of KCC2 by seizures in mature and immature neurons may be one of the age-related factors that protect the neonatal brain against the development of epilepsy.

Original languageEnglish (US)
Pages (from-to)14-18
Number of pages5
JournalEpilepsia
Volume48
Issue numberSUPPL. 5
DOIs
StatePublished - Sep 1 2007

Keywords

  • Adult
  • Chloride cotransporter
  • Epilepsy
  • GABA receptor
  • Hippocampus
  • KCC2
  • Kainic acid
  • NKCC1
  • Neonatal
  • Rat

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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