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The Inhibitory Effects of Interleukin‐6 on Synaptic Plasticity in the Rat Hippocampus Are Associated with an Inhibition of Mitogen‐Activated Protein Kinase ERK
Author(s) -
Tancredi Virginia,
D'Antuono Margherita,
Cafè Carla,
Giovedì Silvia,
Buè Maria Cristina,
D'Arcangelo Giovanna,
Onofri Franco,
Benfenati Fabio
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750634.x
Subject(s) - mapk/erk pathway , long term potentiation , synaptic plasticity , microbiology and biotechnology , kinase , mitogen activated protein kinase kinase , mapk cascade , protein kinase a , biology , chemistry , biochemistry , receptor
Several cytokines have short‐term effects on synaptic transmission and plasticity that are thought to be mediated by the activation of intracellular protein kinases. We have studied the effects of interleukin‐6 (IL‐6) on the expression of paired pulse facilitation (PPF), posttetanic potentiation (PTP), and long‐term potentiation (LTP) in the CA1 region of the hippocampus as well as on the activation of the signal transducer and activator of transcription‐3 (STAT3), the mitogen‐activated protein kinase ERK (MAPK/ERK), and the stress‐activated protein kinase/c‐Jun NH 2 ‐terminal kinase (SAPK/JNK). IL‐6 induced a marked and dose‐dependent decrease in the expression of PTP and LTP that could be counteracted by the simultaneous treatment with the tyrosine kinase inhibitor lavendustin A (LavA) but did not significantly affect PPF. The IL‐6‐induced inhibition of PTP and LTP was accompanied by a simulation of STAT3 tyrosine phosphorylation and an inhibition of MAPK/ERK dual phosphorylation, in the absence of changes in the state of activation of SAPK/JNK. Both effects of IL‐6 on STAT3 and MAPK/ERK activation were effectively counteracted by LavA treatment. The results indicate the tyrosine kinases and MAPK/ERK are involved in hippocampal synaptic plasticity and may represent preferential intracellular targets for the actions of IL‐6 in the adult nervous system.