PMID- 17567802
OWN - NLM
STAT- MEDLINE
DCOM- 20070719
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 24
DP  - 2007 Jun 13
TI  - Brain-derived neurotrophic factor regulates cholesterol metabolism for synapse 
      development.
PG  - 6417-27
AB  - Brain-derived neurotrophic factor (BDNF) exerts multiple biological functions in 
      the CNS. Although BDNF can control transcription and protein synthesis, it still 
      remains open to question whether BDNF regulates lipid biosynthesis. Here we show 
      that BDNF elicits cholesterol biosynthesis in cultured cortical and hippocampal 
      neurons. Importantly, BDNF elicited cholesterol synthesis in neurons, but not in 
      glial cells. Quantitative reverse transcriptase-PCR revealed that BDNF stimulated 
      the transcription of enzymes in the cholesterol biosynthetic pathway. 
      BDNF-induced cholesterol increases were blocked by specific inhibitors of 
      cholesterol synthesis, mevastatin and zaragozic acid, suggesting that BDNF 
      stimulates de novo synthesis of cholesterol rather than the incorporation of 
      extracellular cholesterol. Because cholesterol is a major component of lipid 
      rafts, we investigated whether BDNF would increase the cholesterol content in 
      lipid rafts or nonraft membrane domains. Interestingly, the BDNF-mediated 
      increase in cholesterol occurred in rafts, but not in nonrafts, suggesting that 
      BDNF promotes the development of neuronal lipid rafts. Consistent with this 
      notion, BDNF raised the level of the lipid raft marker protein caveolin-2 in 
      rafts. Remarkably, BDNF increased the levels of presynaptic proteins in lipid 
      rafts, but not in nonrafts. An electrophysiological study revealed that 
      BDNF-dependent cholesterol biosynthesis plays an important role for the 
      development of a readily releasable pool of synaptic vesicles. Together, these 
      results suggest a novel role for BDNF in cholesterol metabolism and synapse 
      development.
FAU - Suzuki, Shingo
AU  - Suzuki S
AD  - Research Institute for Cell Engineering, National Institute of Advanced 
      Industrial Science and Technology, Ikeda, Osaka 563-8577, Japan.
FAU - Kiyosue, Kazuyuki
AU  - Kiyosue K
FAU - Hazama, Shunsuke
AU  - Hazama S
FAU - Ogura, Akihiko
AU  - Ogura A
FAU - Kashihara, Megumi
AU  - Kashihara M
FAU - Hara, Tomoko
AU  - Hara T
FAU - Koshimizu, Hisatsugu
AU  - Koshimizu H
FAU - Kojima, Masami
AU  - Kojima M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 87Z59R7D14 (Filipin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/drug effects
MH  - Biosynthetic Pathways/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cholesterol/*metabolism
MH  - Embryo, Mammalian
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects
MH  - Filipin/metabolism
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Hippocampus/cytology
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*cytology/*drug effects
MH  - Patch-Clamp Techniques/methods
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Receptor, trkB/metabolism
MH  - Synapses/*physiology
PMC - PMC6672445
EDAT- 2007/06/15 09:00
MHDA- 2007/07/20 09:00
PMCR- 2007/12/13
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/07/20 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
PHST- 2007/12/13 00:00 [pmc-release]
AID - 27/24/6417 [pii]
AID - 3232518 [pii]
AID - 10.1523/JNEUROSCI.0690-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Jun 13;27(24):6417-27. doi: 10.1523/JNEUROSCI.0690-07.2007.