PMID- 18287532
OWN - NLM
STAT- MEDLINE
DCOM- 20081112
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 19
IP  - 5
DP  - 2008 May
TI  - Cholesterol loss enhances TrkB signaling in hippocampal neurons aging in vitro.
PG  - 2101-12
AB  - Binding of the neurotrophin brain-derived neurotrophic factor (BDNF) to the TrkB 
      receptor is a major survival mechanism during embryonic development. In the aged 
      brain, however, BDNF levels are low, suggesting that if TrkB is to play a role in 
      survival at this stage additional mechanisms must have developed. We here show 
      that TrkB activity is most robust in the hippocampus of 21-d-old BDNF-knockout 
      mice as well as in old, wild-type, and BDNF heterozygous animals. Moreover, 
      robust TrkB activity is evident in old but not young hippocampal neurons 
      differentiating in vitro in the absence of any exogenous neurotrophin and also in 
      neurons from BDNF -/- embryos. Age-associated increase in TrkB activity 
      correlated with a mild yet progressive loss of cholesterol. This, in turn, 
      correlated with increased expression of the cholesterol catabolic enzyme 
      cholesterol 24-hydroxylase. Direct cause-effect, cholesterol loss-high TrkB 
      activity was demonstrated by pharmacological means and by manipulating the levels 
      of cholesterol 24-hydroxylase. Because reduced levels of cholesterol and 
      increased expression of choleseterol-24-hydroxylase were also observed in the 
      hippocampus of aged mice, changes in cellular cholesterol content may be used to 
      modulate receptor activity strength in vivo, autonomously or as a way to 
      complement the natural decay of neurotrophin production.
FAU - Martin, Mauricio G
AU  - Martin MG
AD  - VIB and Department of Human Genetics, Catholic University of Leuven, B-3000 
      Leuven, Belgium.
FAU - Perga, Simona
AU  - Perga S
FAU - Trovo, Laura
AU  - Trovo L
FAU - Rasola, Andrea
AU  - Rasola A
FAU - Holm, Pontus
AU  - Holm P
FAU - Rantamaki, Tomi
AU  - Rantamaki T
FAU - Harkany, Tibor
AU  - Harkany T
FAU - Castren, Eero
AU  - Castren E
FAU - Chiara, Federica
AU  - Chiara F
FAU - Dotti, Carlos G
AU  - Dotti CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080220
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Detergents)
RN  - 0 (Ligands)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.25 (Cholesterol 24-Hydroxylase)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Membrane/drug effects/enzymology
MH  - Cells, Cultured
MH  - *Cellular Senescence/drug effects
MH  - Cholesterol/*deficiency
MH  - Cholesterol 24-Hydroxylase
MH  - Detergents/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Hippocampus/*cytology/enzymology
MH  - Ligands
MH  - Mice
MH  - Neurons/*cytology/drug effects/*enzymology
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Steroid Hydroxylases/metabolism
PMC - PMC2366859
EDAT- 2008/02/22 09:00
MHDA- 2008/11/13 09:00
PMCR- 2008/06/28
CRDT- 2008/02/22 09:00
PHST- 2008/02/22 09:00 [pubmed]
PHST- 2008/11/13 09:00 [medline]
PHST- 2008/02/22 09:00 [entrez]
PHST- 2008/06/28 00:00 [pmc-release]
AID - E07-09-0897 [pii]
AID - 3330191 [pii]
AID - 10.1091/mbc.e07-09-0897 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2008 May;19(5):2101-12. doi: 10.1091/mbc.e07-09-0897. Epub 2008 
      Feb 20.