Inhibition of LTP-Induced Translation by IL-1β Reduces the Level of Newly Synthesized Proteins in Hippocampal Dendrites

作者：G. Aleph Prieto, Erica D. Smith, Liqi Tong, Michelle M. Nguyen, Carl W. Cotman · 发表于：ACS Chemical Neuroscience · 年份：2019 · DOI：10.1021/acschemneuro.8b00511 · 被引用次数：27 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neuroscience and Neuropharmacology Research、Immune Response and Inflammation

In rodent hippocampus, the inflammatory cytokine interleukin-1β (IL-1β) impairs memory and long-term potentiation (LTP), a major form of plasticity that depends on protein synthesis. A better understanding of the mechanisms by which IL-1β impairs LTP may help identify targets for preventing cognitive deterioration. We tested whether IL-1β inhibits protein synthesis in hippocampal neuron cultures following chemically induced LTP (cLTP). Fluorescent-tagging using click-chemistry showed that IL-1β reduces the level of newly synthesized proteins in proximal dendrites of cLTP stimulated neurons. Relative to controls, in cLTP stimulated neurons, IL-1β inhibited Akt/mTOR signaling, as well as the upregulation of GluA1, an AMPA receptor subunit, and LIMK1, a kinase that promotes actin polymerization. Notably, a novel TIR domain peptidomimetic (EM163) blocked both the activation of p38 and the suppression of cLTP-dependent protein synthesis by IL-1β. Our data support a model where IL-1β suppresses LTP directly in neurons by inhibiting mTOR-dependent translation.