PMID- 23422279
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20220309
IS  - 1549-5485 (Electronic)
IS  - 1072-0502 (Print)
IS  - 1072-0502 (Linking)
VI  - 20
IP  - 3
DP  - 2013 Feb 19
TI  - Estradiol-induced object recognition memory consolidation is dependent on 
      activation of mTOR signaling in the dorsal hippocampus.
PG  - 147-55
LID - 10.1101/lm.026732.112 [doi]
AB  - The mammalian target of rapamycin (mTOR) signaling pathway is an important 
      regulator of protein synthesis and is essential for various forms of hippocampal 
      memory. Here, we asked whether the enhancement of object recognition memory 
      consolidation produced by dorsal hippocampal infusion of 17beta-estradiol (E(2)) is 
      dependent on mTOR signaling in the dorsal hippocampus, and whether E(2)-induced 
      mTOR signaling is dependent on dorsal hippocampal phosphatidylinositol 3-kinase 
      (PI3K) and extracellular signal-regulated kinase (ERK) activation. We first 
      demonstrated that the enhancement of object recognition induced by E(2) was 
      blocked by dorsal hippocampal inhibition of ERK, PI3K, or mTOR activation. We 
      then showed that an increase in dorsal hippocampal ERK phosphorylation 5 min 
      after intracerebroventricular (ICV) E(2) infusion was also blocked by dorsal 
      hippocampal infusion of the three cell signaling inhibitors. Next, we found that 
      ICV infusion of E(2) increased phosphorylation of the downstream mTOR targets S6K 
      (Thr-421) and 4E-BP1 in the dorsal hippocampus 5 min after infusion, and that 
      this phosphorylation was blocked by dorsal hippocampal infusion of inhibitors of 
      ERK, PI3K, and mTOR. Collectively, these data demonstrate for the first time that 
      activation of the dorsal hippocampal mTOR signaling pathway is necessary for E(2) 
      to enhance object recognition memory consolidation and that E(2)-induced mTOR 
      activation is dependent on upstream activation of ERK and PI3K signaling.
FAU - Fortress, Ashley M
AU  - Fortress AM
AD  - Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, 
      USA.
FAU - Fan, Lu
AU  - Fan L
FAU - Orr, Patrick T
AU  - Orr PT
FAU - Zhao, Zaorui
AU  - Zhao Z
FAU - Frick, Karyn M
AU  - Frick KM
LA  - eng
GR  - R01 AG022525/AG/NIA NIH HHS/United States
GR  - AG022525/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - United States
TA  - Learn Mem
JT  - Learning & memory (Cold Spring Harbor, N.Y.)
JID - 9435678
RN  - 0 (Butadienes)
RN  - 0 (Chromones)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Morpholines)
RN  - 0 (Nitriles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (U 0126)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Butadienes/pharmacology
MH  - Chromones/pharmacology
MH  - Estradiol/*pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Female
MH  - Hippocampus/*drug effects
MH  - Injections, Intraventricular
MH  - MAP Kinase Signaling System/drug effects
MH  - Memory/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase 1/drug effects/metabolism
MH  - Morpholines/pharmacology
MH  - Nitriles/pharmacology
MH  - Ovariectomy
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Recognition, Psychology/*drug effects
MH  - Ribosomal Protein S6 Kinases, 90-kDa/physiology
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*drug effects
PMC - PMC3578274
EDAT- 2013/02/21 06:00
MHDA- 2013/08/07 06:00
PMCR- 2014/03/01
CRDT- 2013/02/21 06:00
PHST- 2013/02/21 06:00 [entrez]
PHST- 2013/02/21 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 20/3/147 [pii]
AID - FortressLM026732 [pii]
AID - 10.1101/lm.026732.112 [doi]
PST - epublish
SO  - Learn Mem. 2013 Feb 19;20(3):147-55. doi: 10.1101/lm.026732.112.