Interleukin-1 beta inhibits glutamate release in hippocampus of young, but not aged, rats

Neurobiol Aging. May-Jun 1997;18(3):343-8. doi: 10.1016/s0197-4580(97)80317-x.

Abstract

The proinflammatory cytokine, interleukin-1, is synthesized in neuronal and glial cells and is released in response to stress/injury. IL-1 exerts profound effects on the central nervous system, which include an inhibitory effect on synaptic activity in hippocampus, a brain area expressing a high density of IL-1 receptors. We report that IL-1 beta has an inhibitory effect on KCl-stimulated release of glutamate and KC1-stimulated [45Ca] influx in synaptosomes prepared from hippocampus of 4-month-old rats. These effects were inhibited by the endogenous receptor antagonist, IL-1ra, and by the phospholipase A2 (PLA2) inhibitor, quinacrine, suggesting that IL-1 receptor activation is coupled to PLA2. An inhibitory effect of IL-1 beta on protein kinase C activity was also observed. KC1-induced calcium-dependent release and calcium influx, and protein kinase C activity were significantly decreased in hippocampal synaptosomes prepared from 22-month-old compared to 4-month-old animals. In contrast to the inhibitory effect of IL-1 beta in synaptosomes prepared from young adult animals, no effect was observed on release, calcium influx, or protein kinase C activity in synaptosomes prepared from aged animals. We report that there is an age-related increase in expression of IL-1 beta in hippocampus and propose that this change may underlie the attenuated responses to IL-1 beta in hippocampus of aged animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / drug effects*
  • Animals
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Interleukin-1 / pharmacology*
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Interleukin-1
  • Glutamic Acid