The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Brain cholesterol turnover required for geranylgeraniol production and learning in mice
Abstract
The mevalonate pathway produces cholesterol and nonsterol isoprenoids, such as geranylgeraniol. In the brain, a fraction of cholesterol is metabolized in neurons by the enzyme cholesterol 24-hydroxylase, and this depletion activates the mevalonate pathway. Brains from mice lacking 24-hydroxylase excrete cholesterol more slowly, and the tissue compensates by suppressing the mevalonate pathway. Here we report that this suppression causes a defect in learning. 24-Hydroxylase knockout mice exhibit severe deficiencies in spatial, associative, and motor learning, and in hippocampal long-term potentiation (LTP). Acute treatment of wild-type hippocampal slices with an inhibitor of the mevalonate pathway (a statin) also impairs LTP. The effects of statin treatment and genetic elimination of 24-hydroxylase on LTP are reversed by a 20-min treatment with geranylgeraniol but not by cholesterol. We conclude that cholesterol turnover in brain activates the mevalonate pathway and that a constant production of geranylgeraniol in a small subset of neurons is required for LTP and learning.
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.
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
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902
Regulation of the mevalonate pathway
Goldstein, J. L., & Brown, M. S. (1990) · Nature · doi:10.1038/343425a0 · Cited by 5,394
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Malenka, R. C., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.012 · Cited by 3,968
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
Neurosteroids: endogenous regulators of the GABAA receptor
Belelli, D., & Lambert, J. J. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1703 · Cited by 1,159
The discovery and development of HMG-CoA reductase inhibitors.
Endo, A. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41379-3 · Cited by 847
Importance of AMPA Receptors for Hippocampal Synaptic Plasticity But Not for Spatial Learning
Zamanillo, D., Sprengel, R., Hvalby, Ø., Jensen, V., Burnashev, N., Rozov, A., Kaiser, K. M. M., Köster, H. J., Borchardt, T., Worley, P., et al. (1999) · Science · doi:10.1126/science.284.5421.1805 · Cited by 791
Recycling Endosomes Supply AMPA Receptors for LTP
Park, M., Penick, E. C., Edwards, J. G., Kauer, J. A., & Ehlers, M. D. (2004) · Science · doi:10.1126/science.1102026 · Cited by 730
Lund, E. G., Xie, C., Kotti, T., Turley, S. D., Dietschy, J. M., & Russell, D. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303415200 · Cited by 421
Self-citationHeart Protection Study Collaborative Group (2011) · The Lancet · doi:10.1016/s0140-6736(11)61125-2 · Cited by 373
Erbel-Sieler, C., Dudley, C., Zhou, Y., Wu, X., Estill, S. J., Han, T., Diaz-Arrastia, R., Brunskill, E. W., Potter, S. S., & McKnight, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405310101 · Cited by 178
Xie, C., Lund, E. G., Turley, S. D., Russell, D. W., & Dietschy, J. M. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m300164-jlr200 · Cited by 159
Self-citation
Cited by
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524
Gut microbial molecules in behavioural and neurodegenerative conditions
Needham, B. D., Kaddurah-Daouk, R., & Mazmanian, S. K. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00381-0 · Cited by 379
Cholesterol 24-Hydroxylase: an enzyme of cholesterol turnover in the brain
Russell, D. W., Halford, R. W., Ramirez, D. M. O., Shah, R., & Kotti, T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.072407.103859 · Cited by 317
Self-citationCholesterol in brain disease: Sometimes determinant and frequently implicated
Martín, M. G., Pfrieger, F., & Dotti, C. G. (2014) · The EMBO Reports · doi:10.15252/embr.201439225 · Cited by 304
Oxysterols and neurodegenerative diseases
Björkhem, I., Cedazo-Minguez, A., Leoni, V., & Meaney, S. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.02.001 · Cited by 271
Metadata
- Authors
- Kotti, T. J., Ramirez, D. M. O., Pfeiffer, B. E., Huber, K. M., & Russell, D. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-02-27
- Volume
- 103
- Issue
- 10
- Pages
- 3869-3874
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2008823657
- Cited by
- 261
- References
- 14
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
