relation: http://publicatio.bibl.u-szeged.hu/9335/
title: Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways
creator:  Szegedi Viktor
creator:  Juhász Gábor
creator:  Zhang Xiaoqun
creator:  Barkóczi Balázs
creator:  Qi Hongshi
creator:  Madeira Alexandra
creator:  Kapus Gábor
creator:  Svenningsson Per
creator:  Spedding Michael
creator:  Penke Botond
description: Impairments of cellular plasticity appear to underlie the pathophysiology of major depression. Recently, elevated levels of phosphorylated AMPA receptor were implicated in the antidepressant effect of various drugs. Here, we investigated the effects of an antidepressant, Tianeptine, on synaptic function and GluA1 phosphorylation using murine hippocampal slices and in vivo single-unit recordings. Tianeptine, but not imipramine, increased AMPA receptor-mediated neuronal responses both in vitro and in vivo, in a staurosporine-sensitive manner. Paired-pulse ratio was unaltered by Tianeptine, suggesting a postsynaptic site of action. Tianeptine, 10 μM, enhanced the GluA1-dependent initial phase of LTP, whereas 100 μM impaired the latter phases, indicating a critical role of GluA1 subunit phosphorylation in the excitation. Tianeptine rapidly increased the phosphorylation level of Ser(831)-GluA1 and Ser(845)-GluA1. Using H-89 and KN-93, we show that the activation of both PKA and CaMKII is critical in the effect of Tianeptine on AMPA responses. Moreover, the phosphorylation states of Ser(217/221)-MEK and Thr(183)/Tyr(185)-p42MAPK were increased by Tianeptine and specific kinase blockers of the MAPK pathways (PD 98095, SB 203580 and SP600125) prevented the effects of Tianeptine. Overall these data suggest that Tianeptine potentiates several signaling cascades associated with synaptic plasticity and provide further evidence that a major mechanism of action for Tianeptine is to act as an enhancer of glutamate neurotransmission via AMPA receptors.
date: 2011-12
type: Folyóiratcikk
type: NonPeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/9335/7/Tianeptine_potentiates_AMPA_receptors_SzegediV_NeurochemInt_2011.pdf
identifier:     Szegedi Viktor;  Juhász Gábor;  Zhang Xiaoqun;  Barkóczi Balázs;  Qi Hongshi;  Madeira Alexandra;  Kapus Gábor;  Svenningsson Per;  Spedding Michael;  Penke Botond: Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways.   Neurochemistry international, 59 (8).  pp. 1109-1122.  ISSN 1872-9754 (2011)     
identifier: doi:10.1016/j.neuint.2011.10.008
relation: 1842703
language: eng