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Cited by 87Axon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Cholesterol-mediated Neurite Outgrowth Is Differently Regulated between Cortical and Hippocampal Neurons

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Ko, Mihee, Zou, Kun, Minagawa, Hirohisa, Yu, Wenxin, Gong, Jian-Sheng, Yanagisawa, Katsuhiko, Michikawa, Makoto·2005·Journal of Biological Chemistry
DOI 10.1074/jbc.m509164200
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Abstract

The acquisition of neuronal type-specific morphogenesis is a central feature of neuronal differentiation and has important consequences for region-specific nervous system functions. Here, we report that the cell type-specific cholesterol profile determines the differential modulation of axon and dendrite outgrowths in hippocampal and cerebral cortical neurons in culture. The extent of axon and dendrite outgrowths is greater and the polarity formation occurs earlier in cortical neurons than in hippocampal neurons. The cholesterol concentrations in total homogenate and the lipid rafts from hippocampal neurons are significantly higher than those from cortical neurons. Cholesterol depletion by beta-cyclodextrin markedly enhanced the neurite outgrowth and accelerated the establishment of neuronal polarity in hippocampal neurons, which were similarly observed in nontreated cortical neurons, whereas cholesterol loading had no effects. In contrast, both depletion and loading of cholesterol decreased the neurite outgrowths in cortical neurons. The stimulation of neurite outgrowth and polarity formation induced by cholesterol depletion was accompanied by an enhanced localization of Fyn, a Src kinase, in the lipid rafts of hippocampal neurons. A concomitant treatment with beta-cyclodextrin and a Src family kinase inhibitor, PP2, specifically blocked axon outgrowth but not dendrite outgrowth (both of which were enhanced by beta-cyclodextrin) in hippocampal neurons, suggesting that axon outgrowth modulated by cholesterol is induced in a Fyn-dependent manner. These results suggest that cellular cholesterol modulates axon and dendrite outgrowths and neuronal polarization under culture conditions and also that the difference in cholesterol profile between hippocampal and cortical neurons underlies the difference in neurite outgrowth between these two types of neurons.

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  • Either increased or decreased amounts of sterols can impair neurological function, demanding a tight regulation of brain sterol synthesis.

    “Either increased or decreased amounts of sterols can impair neurological function, demanding a tight regulation of brain sterol synthesis35.”

    From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [35]

    The Results and Discussion (pages not provided) show that both cholesterol loading and depletion reduced neurite outgrowth in cultured cortical neurons, supporting the need for an optimal cholesterol concentration in that setting. The paper does not establish that altered sterol amounts impair neurological function generally or that brain sterol synthesis must be tightly regulated; it says the findings still need confirmation in vivo. (LLM, conf=0.87)

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References 30 · Cited by 87

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Authors
Ko, M., Zou, K., Minagawa, H., Yu, W., Gong, J.-S., Yanagisawa, K., & Michikawa, M.
Corresponding author
Michikawa, Makoto
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-12
Volume
280
Issue
52
Pages
42759-42765
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m509164200
OpenAlex
W1969992151
Cited by
87
References
30
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 9
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
cholesterol, neurite outgrowth, axon growth, dendritic outgrowth, neuronal polarity, hippocampal neurons, cortical neurons, lipid rafts, β-cyclodextrin, Fyn, Src family kinases, PP2, neuronal differentiation
MeSH terms
Protein Phosphatase 2C, Animals, Axons, Brain, Cerebral Cortex, Cholesterol, Detergents, Hippocampus, Lipids, Neurons, Phosphoprotein Phosphatases, Time Factors, Immunoblotting, Octoxynol, src-Family Kinases, Membrane Microdomains, beta-Cyclodextrins, Proto-Oncogene Proteins c-fyn, Rats

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