PMID- 22212527
OWN - NLM
STAT- MEDLINE
DCOM- 20120608
LR  - 20211203
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 11
IP  - 2
DP  - 2012 Apr
TI  - Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by 
      reducing IL-1beta and enhancing NMDA signaling.
PG  - 326-35
LID - 10.1111/j.1474-9726.2011.00791.x [doi]
AB  - Understanding the factors that contribute to age-related cognitive decline is 
      imperative, particularly as age is the major risk factor for several 
      neurodegenerative disorders. Levels of several cytokines increase in the brain 
      during aging, including IL-1beta, whose levels positively correlate with cognitive 
      deficits. Previous reports show that reducing the activity of the mammalian 
      target of rapamycin (mTOR) extends lifespan in yeast, nematodes, Drosophila, and 
      mice. It remains to be established, however, whether extending lifespan with 
      rapamycin is accompanied by an improvement in cognitive function. In this study, 
      we show that 18-month-old mice treated with rapamycin starting at 2 months of age 
      perform significantly better on a task measuring spatial learning and memory 
      compared to age-matched mice on the control diet. In contrast, rapamycin does not 
      improve cognition when given to 15-month-old mice with pre-existing, 
      age-dependent learning and memory deficits. We further show that the 
      rapamycin-mediated improvement in learning and memory is associated with a 
      decrease in IL-1beta levels and an increase in NMDA signaling. This is the first 
      evidence to show that a small molecule known to increase lifespan also 
      ameliorates age-dependent learning and memory deficits.
CI  - (c) 2011 The Authors. Aging Cell (c) 2011 Blackwell Publishing Ltd/Anatomical Society 
      of Great Britain and Ireland.
FAU - Majumder, Smita
AU  - Majumder S
AD  - Department of Physiology, The University of Texas Health Science Center at San 
      Antonio, San Antonio, TX 78229-3900, USA.
FAU - Caccamo, Antonella
AU  - Caccamo A
FAU - Medina, David X
AU  - Medina DX
FAU - Benavides, Adriana D
AU  - Benavides AD
FAU - Javors, Martin A
AU  - Javors MA
FAU - Kraig, Ellen
AU  - Kraig E
FAU - Strong, Randy
AU  - Strong R
FAU - Richardson, Arlan
AU  - Richardson A
FAU - Oddo, Salvatore
AU  - Oddo S
LA  - eng
GR  - K99 ⁄ R00AG29729-4/AG/NIA NIH HHS/United States
GR  - RC2 AG036613-02/AG/NIA NIH HHS/United States
GR  - R01 AG037637-01A1/AG/NIA NIH HHS/United States
GR  - RC2AG036613/AG/NIA NIH HHS/United States
GR  - RC2 AG036613/AG/NIA NIH HHS/United States
GR  - R01 AG037637/AG/NIA NIH HHS/United States
GR  - R00 AG029729/AG/NIA NIH HHS/United States
GR  - R00 AG029729-05/AG/NIA NIH HHS/United States
GR  - R01AG037637/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 - 20120201
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Interleukin-1beta)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Aging
MH  - Animals
MH  - Drosophila melanogaster
MH  - Interleukin-1beta/*metabolism
MH  - Learning/drug effects
MH  - Memory Disorders/*prevention & control
MH  - Mice
MH  - N-Methylaspartate/metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3306461
MID - NIHMS347105
EDAT- 2012/01/04 06:00
MHDA- 2012/06/09 06:00
PMCR- 2013/04/01
CRDT- 2012/01/04 06:00
PHST- 2012/01/04 06:00 [entrez]
PHST- 2012/01/04 06:00 [pubmed]
PHST- 2012/06/09 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 10.1111/j.1474-9726.2011.00791.x [doi]
PST - ppublish
SO  - Aging Cell. 2012 Apr;11(2):326-35. doi: 10.1111/j.1474-9726.2011.00791.x. Epub 
      2012 Feb 1.