The inhibitory effect of interleukin-1beta on long-term potentiation is coupled with increased activity of stress-activated protein kinases

J Neurosci. 2000 Sep 15;20(18):6811-9. doi: 10.1523/JNEUROSCI.20-18-06811.2000.

Abstract

Long-term potentiation (LTP) in perforant path-granule cell synapses is decreased in aged rats, stressed rats, and rats injected intracerebroventricularly with the proinflammatory cytokine interleukin-1beta (IL-1beta). One factor that is common to these experimental conditions is an increase in the concentration of IL-1beta in the dentate gyrus, suggesting a causal relationship between the compromise in LTP and increased IL-1beta concentration. In this study, we have investigated the downstream consequences of an increase in IL-1beta concentration and report that the reduced LTP in rats injected intracerebroventricularly with IL-1beta was accompanied by a decrease in KCl-stimulated glutamate release in synaptosomes prepared from dentate gyrus, although unstimulated glutamate release was increased. These changes were paralleled by increased activity of the stress-activated kinases, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. Intracerebroventricular injection of IL-1beta increased reactive oxygen species production in hippocampal tissue, whereas IL-1beta and H(2)O(2) increased activities of both JNK and p38 in vitro. Dietary manipulation with antioxidant vitamins E and C blocked the increase in reactive oxygen species production, the stimulation of JNK and p38 activity, the attenuation of glutamate release, and the IL-1beta-induced inhibitory of LTP. We propose that IL-1beta stimulates activity of stress-activated kinases, which in turn may inhibit glutamate release and result in compromised LTP and that these actions are a consequence of increased production of reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / analysis
  • Dietary Supplements
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Glutamic Acid / metabolism
  • Hippocampus / chemistry
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neural Inhibition / drug effects
  • Potassium Chloride / administration & dosage
  • Protein Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Synapses / drug effects
  • Synaptosomes / metabolism
  • Vitamin E / administration & dosage
  • Vitamin E / analysis
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Interleukin-1
  • Reactive Oxygen Species
  • Vitamin E
  • Glutamic Acid
  • Potassium Chloride
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Ascorbic Acid