Inhibition of LTP-Induced Translation by IL-1β
Reduces the Level of Newly Synthesized Proteins in Hippocampal Dendrites
Version 2 2019-02-09, 00:43
Version 1 2019-02-04, 14:40
Posted on 2019-02-09 - 00:43
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.
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Prieto, G. Aleph; Smith, Erica D.; Tong, Liqi; Nguyen, Michelle; Cotman, Carl W. (2019). Inhibition of LTP-Induced Translation by IL-1β
Reduces the Level of Newly Synthesized Proteins in Hippocampal Dendrites. ACS Publications. Collection. https://doi.org/10.1021/acschemneuro.8b00511
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AUTHORS (5)
GP
G. Aleph Prieto
ES
Erica D. Smith
LT
Liqi Tong
MN
Michelle Nguyen
CC
Carl W. Cotman