An immunosuppressant, FK506, protects against neuronal dysfunction and death but has no effect on electrographic and behavioral activities induced by systemic kainate

A. Moriwaki, Y. F. Lu, K. Tomizawa, H. Matsui

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Kainate is a potent agonist of an excitatory amino acid receptor subtype in the central nervous system, and muses neuronal death in several regions of the brain. Neurons are preferentially killed in the hippocampus, especially in the CA1 region, by systemic administration of kainate. It is speculated that functional alterations occur in the neurons preceding death. We examined the effect of FK506 on kainate-induced neuronal death and functional alterations in the rat hippocampal CA1 region. FK506 had no effect on electrographic and behavioral seizure activities induced by kainate; however, it prevented neuronal death measured seven days after administration. Although neither death nor morphological alterations of neurons were observed in the CA1 region 24 h after administration, the neurons exhibited decreased excitatory postsynaptic potentials and enhanced long-term potentiation. This functional alteration was not detected in the rats administered FK506 prior to kainate. Taken together, these observations indicate that functional alteration precedes neuronal death in rats systemically administered kainate and that FK506 prevents both. It is suggested that FK506 exerts its neuroprotective effect not by attenuating electrographic and behavioral seizure activities, but by protecting neurons from kainate-induced functional disorders.

Original languageEnglish
Pages (from-to)855-865
Number of pages11
JournalNeuroscience
Volume86
Issue number3
DOIs
Publication statusPublished - Jun 8 1998

Keywords

  • Cell death
  • FK506
  • Fiber volley
  • Hippocampus
  • Kainate
  • Long-term potentiation

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'An immunosuppressant, FK506, protects against neuronal dysfunction and death but has no effect on electrographic and behavioral activities induced by systemic kainate'. Together they form a unique fingerprint.

  • Cite this