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Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
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Brain-derived neurotrophic factor regulates cholesterol metabolism for synapse development.

Shingo Suzuki1, Kazuyuki Kiyosue, Shunsuke Hazama

  • 1Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka 563-8577, Japan.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|June 15, 2007
PubMed
Summary

Brain-derived neurotrophic factor (BDNF) stimulates cholesterol synthesis in neurons, enhancing lipid rafts and promoting synapse development. This highlights a novel role for BDNF in neuronal lipid metabolism and function.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Brain-derived neurotrophic factor (BDNF) is crucial for central nervous system (CNS) functions.
  • BDNF's role in regulating lipid biosynthesis, particularly cholesterol synthesis, remains largely unexplored.

Purpose of the Study:

  • To investigate whether BDNF regulates cholesterol biosynthesis in neurons.
  • To determine the impact of BDNF-induced cholesterol synthesis on neuronal lipid rafts and synapse development.

Main Methods:

  • Primary neuronal cultures (cortical and hippocampal) were treated with BDNF.
  • Quantitative reverse transcriptase-PCR (qRT-PCR) was used to analyze gene expression of cholesterol biosynthetic enzymes.
  • Cholesterol synthesis inhibitors (mevastatin, zaragozic acid) were employed.
  • Lipid raft and non-raft membrane domains were isolated and analyzed for cholesterol and protein content.
  • Electrophysiological studies assessed synaptic vesicle pool development.

Main Results:

  • BDNF significantly increased cholesterol biosynthesis specifically in neurons, not glial cells.
  • BDNF upregulated the transcription of key enzymes in the cholesterol biosynthetic pathway.
  • The BDNF-mediated cholesterol increase was localized to lipid rafts, suggesting enhanced lipid raft development.
  • BDNF elevated presynaptic protein levels within lipid rafts.
  • BDNF-dependent cholesterol synthesis was essential for the development of a readily releasable pool of synaptic vesicles.

Conclusions:

  • BDNF plays a novel role in regulating neuronal cholesterol metabolism.
  • BDNF promotes the formation and development of neuronal lipid rafts.
  • BDNF-induced cholesterol synthesis is critical for synapse development and function.