Cholesterol Biosynthesis and Uptake in Developing Neurons

Thiago C. Genaro-Mattos, Allison Anderson, Luke B. Allen, Zeljka Korade, Károly Mirnics

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Brain cholesterol biosynthesis, a separate and distinct process from whole-body cholesterol homeostasis, starts during embryonic development. To gain a better understanding of the neuronal and glial contributions to the brain cholesterol pool, we studied this process in control, Dhcr7-/-, and Dhcr24-/- cell cultures. Our LC-MS/MS method allowed us to measure several different sterol intermediates and cholesterol during neuronal differentiation. We found that developing cortical neurons rely on endogenous cholesterol synthesis and utilize ApoE-complexed cholesterol and sterol precursors from their surroundings. Both developing neurons and astrocytes release cholesterol into their local environment. Our studies also uncovered that developing neurons produced significantly higher amounts of cholesterol per cell than the astrocytes. Finally, we established that both neurons and astroglia preferentially use the Bloch sterol biosynthesis pathway, where desmosterol is the immediate precursor to cholesterol. Overall, our studies suggest that endogenous sterol synthesis in developing neurons is a critical and complexly regulated homeostatic process during brain development.

Original languageEnglish (US)
Pages (from-to)3671-3681
Number of pages11
JournalACS Chemical Neuroscience
Volume10
Issue number8
DOIs
StatePublished - Aug 21 2019

Keywords

  • Dhcr24
  • Dhcr7
  • LC-MS/MS
  • Sterol biosynthesis
  • astrocytes
  • cholesterol
  • desmosterol
  • developing neurons

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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