The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Cholesterol Biosynthesis and Uptake in Developing Neurons
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Astrocytes produce excess cholesterol and secrete most of the produced cholesterol for use by neurons7.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [7]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Dietschy, J. M., & Turley, S. D. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r400004-jlr200 · Cited by 1,095
Cholesterol metabolism in the brain
Dietschy, J. M., & Turley, S. D. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00003 · Cited by 906
Cholesterol metabolism and homeostasis in the brain
Zhang, J., & Liu, Q. (2015) · Protein & Cell · doi:10.1007/s13238-014-0131-3 · Cited by 686
Biosynthesis of Cholesterol and Other Sterols
Nes, W. D. (2011) · Chemical Reviews · doi:10.1021/cr200021m · Cited by 659
A newly recognized syndromeof multiple congenital anomalies
Smith, D. W., Lemli, L., & Opitz, J. M. (1964) · The Journal of Pediatrics · doi:10.1016/s0022-3476(64)80264-x · Cited by 650
The Biological Synthesis of Cholesterol
Bloch, K. (1965) · Science · doi:10.1126/science.150.3692.19 · Cited by 562
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516
Malformation syndromes caused by disorders of cholesterol synthesis
Porter, F. D., & Herman, G. E. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r009548 · Cited by 473
Waterham, H. R., Koster, J., Romeijn, G. J., Hennekam, R. C. M., Vreken, P., Andersson, H. C., FitzPatrick, D. R., Kelley, R. I., & Wanders, R. J. A. (2001) · The American Journal of Human Genetics · doi:10.1086/323473 · Cited by 355
Lipid rafts, cholesterol, and the brain
Korade, Z., & Kenworthy, A. K. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.02.019 · Cited by 342
Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron
Goritz, C., Mauch, D. H., & Pfrieger, F. W. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.02.006 · Cited by 330
Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management
Porter, F. D. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.10 · Cited by 318
Outsourcing in the brain: Do neurons depend on cholesterol delivery by astrocytes?
Pfrieger, F. W. (2003) · BioEssays · doi:10.1002/bies.10195 · Cited by 308
Cholesterol and the Biology of Alzheimer's Disease
Wolozin, B. (2004) · Neuron · doi:10.1016/s0896-6273(03)00840-7 · Cited by 275
Lipid Compositions of Different Regions of the Human Brain During Aging
Söderberg, M. P., Edlund, C., Kristensson, K., & Dallner, G. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb01889.x · Cited by 269
Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism
Ferris, H. A., Perry, R. J., Moreira, G. V., Shulman, G. I., Horton, J. D., & Kahn, C. R. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620506114 · Cited by 246
Kandutsch, A. A., & Russell, A. E. (1960) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64608-3 · Cited by 217
Mitsche, M. A., McDonald, J. G., Hobbs, H. H., & Cohen, J. C. (2015) · eLife · doi:10.7554/elife.07999 · Cited by 212
Enzymes in the Conversion of Cholesterol into Bile Acids
Norlin, M., & Wikvall, K. (2007) · Current Molecular Medicine · doi:10.2174/156652407780059168 · Cited by 188
Clinical phenotype of desmosterolosis
FitzPatrick, D. R., Keeling, J. W., Evans, M. J., Kan, A. E., Bell, J. E., Porteous, M. E., Mills, K. A., Winter, R. M., & Clayton, P. T. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980113)75:2 · Cited by 172
Michikawa, M., & Yanagisawa, K. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722278.x · Cited by 140
Rapp, A., Gmeiner, B., & Hüttinger, M. (2006) · Biochimie · doi:10.1016/j.biochi.2005.10.007 · Cited by 130
Survival of adult neurons lacking cholesterol synthesis in vivo
Fünfschilling, U., Saher, G., Xiao, L., Möbius, W., & Nave, K.-A. (2007) · BMC Neuroscience · doi:10.1186/1471-2202-8-1 · Cited by 120
Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay
Andersson, H. C., Kratz, L. E., & Kelley, R. I. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.b.10873 · Cited by 118
Valenza, M., Leoni, V., Tarditi, A., Mariotti, C., Björkhem, I., Di Donato, S., & Cattaneo, E. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.07.004 · Cited by 115
Porter, F. D. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3069 · Cited by 108
The lipid compositions of different regions of rat brain during development and aging
Zhang, Y., Appelkvist, E., Kristensson, K., & Dallner, G. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00076-0 · Cited by 101
Critical Time Window of Neuronal Cholesterol Synthesis during Neurite Outgrowth
Fünfschilling, U., Jockusch, W. J., Sivakumar, N., Möbius, W., Corthals, K., Li, S., Quintes, S., Kim, Y., Schaap, I. A. T., Rhee, J., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1352-11.2012 · Cited by 97
3β-Hydroxysterol Δ7-reductase and the Smith–Lemli–Opitz syndrome
Correa-Cerro, L. S., & Porter, F. D. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.09.017 · Cited by 92
DHCEO accumulation is a critical mediator of pathophysiology in a Smith–Lemli–Opitz syndrome model
Xu, L., Mirnics, K., Bowman, A. B., Liu, W. X., Da, J., Porter, N. A., & Korade, Ž. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.011 · Cited by 92
Self-citationXie, C., Turley, S. D., & Dietschy, J. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.11992 · Cited by 92
Cholesterol--Making or Breaking the Synapse
Barres, B. A., & Smith, S. J. (2001) · Science · doi:10.1126/science.1066724 · Cited by 90
Ačimovič, J., Lövgren‐Sandblom, A., Monostory, K., Rozman, D., Goličnik, M., Lütjohann, D., & Björkhem, I. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2009.05.050 · Cited by 87
Ko, M., Zou, K., Minagawa, H., Yu, W., Gong, J.-S., Yanagisawa, K., & Michikawa, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509164200 · Cited by 87
Segoviano-Mendoza, M. A., la Cruz, M. C.-D., Salas-Pacheco, J. M., Vázquez-Alaníz, F., Llave-León, O. L., Castellanos-Juárez, F. X., Hernández, J. E. M., Barraza-Salas, M., Miranda-Morales, E. G., Arias-Carrión, Ó., et al. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1596-z · Cited by 83
Correa-Cerro, L. S., Wassif, C. A., Kratz, L., Miller, G. F., Munasinghe, J. P., Grinberg, A., Fliesler, S. J., & Porter, F. D. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl003 · Cited by 75
Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series
Cham, S., Koslik, H. J., & Golomb, B. A. (2015) · Drug Safety - Case Reports · doi:10.1007/s40800-015-0024-2 · Cited by 71
Korade, Z., Kim, H.-Y. H., Tallman, K. A., Liu, W., Koczok, K., Balogh, I., Xu, L., Mirnics, K., & Porter, N. A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01696 · Cited by 65
Self-citationKim, H.-Y. H., Korade, Z., Tallman, K. A., Liu, W., Weaver, C. D., Mirnics, K., & Porter, N. A. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00054 · Cited by 53
Self-citationLiu, W., Xu, L., Lamberson, C. R., Haas, D., Korade, Ž., & Porter, N. A. (2013) · Journal of Lipid Research · doi:10.1194/jlr.d043877 · Cited by 51
Korade, Ž., Mi, Z., Portugal, C. F., & Schor, N. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.026 · Cited by 51
The Age-dependent Elevation of miR-335-3p Leads to Reduced Cholesterol and Impaired Memory in Brain
Raihan, M. O., Brishti, A., Molla, M. R., Li, W., Zhang, Q., Xu, P., Khan, M. I., Zhang, J., & Liu, Q. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.08.003 · Cited by 44
Genaro‐Mattos, T. C., Tallman, K. A., Allen, L. B., Anderson, A. C., Mirnics, K., Korade, Ž., & Porter, N. A. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.04.029 · Cited by 43
Self-citationMast, N., Lin, J. B., Anderson, K. W., Björkhem, I., & Pikuleva, I. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187168 · Cited by 37
Disentangling the genetic overlap between cholesterol and suicide risk
Knowles, E. E. M., Curran, J. E., Meikle, P. J., Huynh, K., Mathias, S. R., Göring, H. H. H., VandeBerg, J. L., Mahaney, M. C., Jalbrzikowski, M., Mosior, M. K., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0162-1 · Cited by 35
PACAP signaling to DREAM: A cAMP-Dependent Pathway that Regulates Cortical Astrogliogenesis
Vallejo, M. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8055-2 · Cited by 31
Desmosterolosis and desmosterol homeostasis in the developing mouse brain
Allen, L. B., Genaro‐Mattos, T. C., Porter, N. A., Mirnics, K., & Korade, Z. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12088 · Cited by 31
Self-citationVulnerability of DHCR7+/− mutation carriers to aripiprazole and trazodone exposure
Korade, Ž., Genaro‐Mattos, T. C., Tallman, K. A., Liu, W., Garbett, K. A., Koczok, K., Balogh, I., Mirnics, K., & Porter, N. A. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m079475 · Cited by 27
Self-citationNovel cell separation method for molecular analysis of neuron-astrocyte co-cultures
Goudriaan, A., Camargo, N., Carney, K. E., Oliet, S. H. R., Smit, A. B., & Verheijen, M. H. G. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00012 · Cited by 24
Flagged first, then by citations
Research works printed but not linked: 1
- Allen L. B., 2019, J. Inherit Metab Dis
Cited by
Sorted by citations
Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects
Feringa, F. M., & van der Kant, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.690372 · Cited by 226
Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases
Yang, D., Wang, X., Zhang, L., Fang, Y., Zheng, Q., Liu, X., Yu, W., Chen, S., Ying, J., & Hua, F. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00828-0 · Cited by 179
Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory
Li, X., Zhang, J., Li, D., He, C., He, K., Xue, T., Wan, L., Zhang, C., & Liu, Q. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.005 · Cited by 165
Goldstein, L. B., Toth, P. P., Dearborn, J. L., Giugliano, R. P., Hirsh, B. J., Peña, J. M., Selim, M. H., & Woo, D. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atv.0000000000000164 · Cited by 99
Impaired cholesterol metabolism, neurons, and neuropsychiatric disorders
Cheon, S. Y. (2023) · Experimental Neurobiology · doi:10.5607/en23010 · Cited by 67
Metadata
- Authors
- Genaro-Mattos, T. C., Anderson, A., Allen, L. B., Korade, Z., & Mirnics, K.
- Affiliations
- Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States
- University of Nebraska Medical Center (US)
- Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
- Corresponding author
- Mirnics, Károly
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-06-07
- Volume
- 10
- Issue
- 8
- Pages
- 3671-3681
- ISSN
- 1948-7193 (ISSN-L)
- PMC
- PMC7184320
- OpenAlex
- W2950398114
- Cited by
- 117
- References
- 49
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 19 · 2023: 18 · 2022: 22 · 2021: 12 · 2020: 8
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH110636, R01 MH067234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Keywords
- cholesterol absorption, developing neurons, cortical neurons, astrocytes, DHCR7, DHCR24, sterol intermediates, desmosterol, neuronal differentiation, brain development, cholesterol homeostasis
- MeSH terms
- Animals, Astrocytes, Biological Transport, Brain, Cholesterol, Chromatography, Liquid, Neurons, Sterols, Mice, Tandem Mass Spectrometry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
