mTOR inhibitor rapamycin suppresses striatal post-ischemic LTP

被引：22

作者：

Ghiglieri, Veronica ^{[1
]}

Pendolino, Valentina ^{[1
]}

Bagetta, Vincenza ^{[1
]}

Sgobio, Carmelo ^{[1
]}

Calabresi, Paolo ^{[1
,2
]}

Picconi, Barbara ^{[1
]}

机构：

[1] Fdn Santa Lucia IRCCS, I-00143 Rome, Italy

[2] Univ Perugia, Neurol Clin, Osped S Maria Misericordia, I-06156 Perugia, Italy

来源：

EXPERIMENTAL NEUROLOGY | 2010年 / 226卷 / 02期

关键词：

Stroke; Oxygen and glucose deprivation; Synaptic plasticity; Striatum; LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; BRAIN; PHOSPHORYLATION; METABOLISM; ACTIVATION; ISCHEMIA; AKT;

D O I：

10.1016/j.expneurol.2010.09.012

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The two complexes of the mammalian target of rapamycin (mTOR), mTORC1 and mTORC2, have central functions in the integration of both extracellular and intracellular signals that are also critical players in the induction of post-ischemic long-term potentiation (i-LTP), a pathological form of plasticity inducible in striatal medium spiny neurons (MSNs) after a brief episode of in vitro ischemia. To evaluate the involvement of mTOR complexes during ischemia we analyzed the time course of i-LTP by intracellular recordings of MSNs from corticostriatal slices incubated with 1 mu M mTOR inhibitor rapamycin. Although rapamycin did not affect the amplitude and duration of ischemia-induced membrane depolarization it fully prevented i-LTP, leaving unaffected the capability to undergo activity-dependent LTP following high-frequency stimulation of corticostriatal fibers. The present results argue for a role of mTOR complex in i-LTP and suggest that rapamycin, by selectively blocking i-LTP, represents a promising therapeutic tool to limit cellular damage after ischemic brain insult. (c) 2010 Elsevier Inc. All rights reserved.

引用

页码：328 / 331

页数：4

共 15 条

[1] Acetyl-L-Carnitine selectively prevents post-ischemic LTP via a possible action on mitochondrial energy metabolism [J].