Blocking mTORC1 activity by rapamycin leads to impairment of spatial memory retrieval but not acquisition in C57BL/6J mice.
Although the involvement of the mTOR (mammalian target of rapamycin) system in memory processes has been reported, information on the effect of rapamycin on spatial learning and memory is limited. It was therefore the aim of the study to show the effect of parenteral rapamycin administration to C57BL/6J mice on performance in the multiple T-maze (MTM) and to determine hippocampal mTOR activity. Rapamycin-treated and -untreated/trained/probed mice are the main part of the experiment considering retrieval and acquisition or consolidation of spatial memory. Six hours following euthanasia hippocampi were extirpated and used for evaluation of mTOR activity as represented by hippocampal levels of S6 protein and its phosphorylated active form (phospho S6 protein, S240,244), a read out of mTOR complex 1 activity. Mice given i.p. rapamycin learned the task of the MTM but failed at the probe trial, showing absence of the phosphorylated active form of S6 protein, indicating inhibition of mTOR activity. Herein, impairing effects of rapamycin on retrieval but not on acquisition or consolidation of spatial memory are shown. Deficient memory retrieval was paralleled by inhibition of mTOR complex 1 activity. The current study extends knowledge on rapamycin in memory mechanisms and challenges work on deeper insights into the role of mTOR in different phases of memory formation and retrieval.
Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria.
Alev
A
Deli
Katharina
K
Schipany
Margit
M
Rosner
Harald
H
Höger
Arnold
A
Pollak
Lin
L
Li
Markus
M
Hengstschläger
Gert
G
Lubec
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D000076222:Mechanistic Target of Rapamycin Complex 1; D011939:Mental Recall / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D046912:Multiprotein Complexes; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000037:antagonists & inhibitors*; D038601:Ribosomal Protein S6 / Q000378:metabolism; D045442:Rotarod Performance Test / Q000379:methods; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D004791:Enzyme Inhibitors; D046912:Multiprotein Complexes; D011506:Proteins; D038601:Ribosomal Protein S6; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus