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Cited by 120Cholesterol and Lipid MetabolismCancer, Lipids, and MetabolismSphingolipid Metabolism and Signaling

Survival of adult neurons lacking cholesterol synthesis in vivo

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Fünfschilling, Ursula, Saher, Gesine, Xiao, Le, Möbius, Wiebke, Nave, Klaus-Armin·2007·BMC Neuroscience
DOI 10.1186/1471-2202-8-1PMC PMC1769390
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Abstract

BACKGROUND: Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. RESULTS: Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. CONCLUSION: We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

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  • Astrocytes synthesize cholesterol at a higher rate than neurons and transfer excess cholesterol to neurons.

    “strong evidence suggests that astrocytes synthesize cholesterol at a higher rate than neurons and transfer their excess cholesterol to neurons [38, 40].”

    From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [38]

    The Background describes astrocytes as presumed net cholesterol producers, and the Discussion says adult neurons may rely on glial cholesterol, with astrocytes among the likely suppliers. The paper does not establish that astrocytes synthesize cholesterol at a higher rate than neurons or that the cholesterol they supply is excess. (LLM, conf=0.86)

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Sorted by citations

Authors
Fünfschilling, U., Saher, G., Xiao, L., Möbius, W., & Nave, K.-A.
Affiliations
Max Planck Institute of Experimental Medicine (DE)
Corresponding author
Fünfschilling, Ursula
ORCID
Venue
BMC Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2007-01-02
Volume
8
Issue
1
Pages
1-1
ISSN
1471-2202 (ISSN-L)
DOI
10.1186/1471-2202-8-1
PMC
PMC1769390
OpenAlex
W1496189784
Cited by
120
References
3
Citations by year
2026: 3 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 16 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 8
FWCI
7.65
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
Deutsche Forschungsgemeinschaft (SFB523)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
cholesterol biosynthesis, adult neurons, neuronal survival, squalene synthase, FDFT1, cerebellar granule cells, precerebellar nuclei, cholesterol absorption, brain cholesterol metabolism, conditional gene inactivation, synaptic ultrastructure, motor coordination
MeSH terms
Animals, Cell Line, Cell Survival, Cholesterol, Neurons, Farnesyl-Diphosphate Farnesyltransferase, Mice, Knockout, Mice

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