Repetitive febrile seizures in rat pups cause long-lasting deficits in synaptic plasticity and NR2A tyrosine phosphorylation

Ying Chao Chang, Yu Min Kuo, A. Min Huang, Chao Ching Huang

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Adult rats with early-life frequently repetitive febrile seizures (FRFS), but not single febrile seizure (SFS), exhibited impaired performance in inhibitory avoidance tasks but without significant hippocampal neuronal loss. The mechanisms of long-term memory impairment in the hippocampus of adult rats with early-life FRFS remain unknown. Using a heated-air febrile seizures (FS) paradigm, male rat pups were subjected to single or nine episodes of brief FS at days 10 to 12 postpartum. We found that early-life FRFS led to long-term bidirectional modulation in hippocampal synaptic plasticity, i.e., impaired long-term potentiation and facilitated long-term depression. Three hours after inhibitory avoidance training, phosphorylation of hippocampal extracellular signal-regulated kinase (ERK) 1/2 was significantly less in the FRFS group than in controls. Furthermore, there was a selective alteration in NMDA receptor-mediated ERK1/2 phosphorylation in the hippocampus of the FRFS group. Although the expression levels of NMDA receptor subunits and interaction of NMDA receptor and postsynaptic density 95 did not alter quantitatively, there was a specific alteration in NR2A, but not NR2B, subunit tyrosine phosphorylation after NMDA stimulation in the FRFS group. These data offer a potential molecular explanation for the hippocampus-dependent memory deficits observed in the rats with early-life FRFS.

Original languageEnglish
Pages (from-to)466-475
Number of pages10
JournalNeurobiology of Disease
Volume18
Issue number3
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

Keywords

  • ERK
  • Febrile seizures
  • Hippocampus
  • Long-term depression
  • Long-term potentiation
  • Memory
  • NMDA
  • NR2A subunits of NMDA receptors
  • NR2B subunits of NMDA receptors
  • Postsynaptic density-95

ASJC Scopus subject areas

  • Neurology

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