Interleukin-1 beta modulates AMPA receptor expression and phosphorylation in hippocampal neurons.
Interleukin (IL)-1beta is a pro-inflammatory cytokine involved in modulating inflammation and stress responses in the brain. Central administration of IL-1beta impairs both memory functions and long-term potentiation (LTP) induction. However, the molecular events responsible for the downstream effects of IL-1beta are not fully understood. Given the potential regulatory role of IL-1beta in LTP, we assessed whether IL-1beta influences surface expression and phosphorylation of glutamate receptors. We found that IL-1beta, but not IL-10 or tumour necrosis factor (TNF)-alpha, down-regulated the surface expression and Ser831 phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1. Agents that block IL-1beta receptor activity abolished these effects. In contrast, no change in the surface expression of the N-methyl-d-aspartate (NMDA) receptor subunit NR1 was observed. The inhibition of NMDA receptor activity or depletion of extracellular calcium blocked IL-1beta effects on GluR1 phosphorylation and surface expression. NMDA-mediated calcium influx was also regulated by IL-1beta. These findings suggest that IL-1beta selectively regulates AMPA receptor phosphorylation and surface expression through extracellular calcium and an unknown mechanism involving NMDA receptor activity.
Lai
Aaron Y
AY
Department of Psychiatry, Neurochemical Research Unit, University of Alberta, Canada.
Swayze
Richard D
RD
El-Husseini
Alaa
A
Song
Cai
C
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000502:physiology*; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D007375:Interleukin-1; D021122:Protein Subunits; D018091:Receptors, AMPA