TY - JOUR
T1 - MTOR inhibitor rapamycin suppresses striatal post-ischemic LTP
AU - Ghiglieri, Veronica
AU - Pendolino, Valentina
AU - Bagetta, Vincenza
AU - Sgobio, Carmelo
AU - Calabresi, Paolo
AU - Picconi, Barbara
PY - 2010/12
Y1 - 2010/12
N2 - 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 1μM 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.
AB - 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 1μM 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.
KW - Oxygen and glucose deprivation
KW - Striatum
KW - Stroke
KW - Synaptic plasticity
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U2 - 10.1016/j.expneurol.2010.09.012
DO - 10.1016/j.expneurol.2010.09.012
M3 - Article
C2 - 20854816
AN - SCOPUS:77958469768
VL - 226
SP - 328
EP - 331
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -