Release of amyloid beta-protein precursor derivatives by electrical depolarization of rat hippocampal slices
Open accessAbstract
Proteolytic processing of the beta-amyloid protein precursor (APP) is regulated by cell-surface receptors. To determine whether neurotransmitter release in response to neuronal activation regulates APP processing in brain, we electrically depolarized superfused rat hippocampal slices and measured soluble APP derivatives released into the superfusate. Electrical depolarization caused a rapid increase in the release of both neurotransmitters and amino-terminal APP cleavage products. These derivatives lacked the APP carboxyl terminus and were similar to those found in both cell culture media and human cerebrospinal fluid. Superfusate proteins including lactate dehydrogenase were not changed by electrical depolarization. The release of amino-terminal APP derivatives increased with increasing stimulation frequencies from 0 to 30 Hz. The increased release was inhibited by the sodium-channel antagonist tetrodotoxin, suggesting that action-potential formation mediates the release of large amino-terminal APP derivatives. These results suggest that neuronal activity regulates APP processing in the mammalian brain.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
Molecular diversity of glutamate receptors and implications for brain function
Nakanishi, S. (1992) · Science · doi:10.1126/science.1329206 · Cited by 2,543 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731 · see citing works
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447 · see citing works
Cleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., & Ward, P. J. (1990) · Science · doi:10.1126/science.2111583 · Cited by 1,403 · see citing works
Koh, J. Y., & Choi, D. W. (1987) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(87)90041-0 · Cited by 1,267 · see citing works
Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein
Weidemann, A., König, G., Bunke, D., Fischer, P. Q., Salbaum, J. M., Masters, C. L., & Beyreuther, K. T. (1989) · Cell · doi:10.1016/0092-8674(89)90177-3 · Cited by 1,233 · see citing works
Haass, C., Koo, E., Mellon, A., Hung, A. Y., & Selkoe, D. (1992) · Nature · doi:10.1038/357500a0 · Cited by 901 · see citing works
Nitsch, R. M., Slack, B. E., Wurtman, R. J., & Growdon, J. H. (1992) · Science · doi:10.1126/science.1411529 · Cited by 898 · see citing works
Self-citationEvidence that β-Amyloid Protein in Alzheimer's Disease Is Not Derived by Normal Processing
Sisodia, S. S., Koo, E. H., Beyreuther, K. T., Unterbeck, A., & Price, D. L. (1990) · Science · doi:10.1126/science.1691865 · Cited by 894 · see citing works
Processing of the amyloid protein precursor to potentially amyloidogenic derivatives.
Golde, T., Estus, S., Younkin, L., Selkoe, D., & Younkin, S. (1992) · Science · doi:10.1126/science.1738847 · Cited by 710 · see citing works
Selkoe, D. J., Podlisny, M. B., Joachim, C. L., Vickers, E., Lee, G. S., Fritz, L. C., & Oltersdorf, T. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.19.7341 · Cited by 579 · see citing works
Buxbaum, J. D., Oishi, M., Chen, H. I., Pinkas‐Kramarski, R., JAFFE, E. A., Gandy, S., & Greengard, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10075 · Cited by 558 · see citing works
Characteristics of CA1 neurons recorded intracellularly in the hippocampalin vitro slice preparation
Schwartzkroin, P. A. (1975) · Brain Research · doi:10.1016/0006-8993(75)90817-3 · Cited by 506 · see citing works
Potentially Amyloidogenic, Carboxyl-Terminal Derivatives of the Amyloid Protein Precursor
Estus, S., Golde, T. E., Kunishita, T., Blades, D. A., Lowery, D. E., Eisen, M., Usiak, M., QU, X., Tabira, T., Greenberg, B., et al. (1992) · Science · doi:10.1126/science.1738846 · Cited by 431 · see citing works
Alzheimer's Disease: a Cell Biological Perspective
Kosik, K. S. (1992) · Science · doi:10.1126/science.1589757 · Cited by 282 · see citing works
Voltage-sensitive ion channels
Jan, L. Y., & Jan, Y. N. (1989) · Cell · doi:10.1016/0092-8674(89)90979-3 · Cited by 264 · see citing works
Palmert, M. R., Podlisny, M. B., Witker, D. S., Oltersdorf, T., Younkin, L. H., Selkoe, D. J., & Younkin, S. G. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6338 · Cited by 254 · see citing works
Maire, J. C., & Wurtman, R. J. (1985) · PubMed · Cited by 81 · see citing works
Self-citationIncubation of Tissue Slices in the Absence of Ca2+ and Mg2+ Can Cause Nonspecific Damage
Lónárt, G., & Zigmond, M. J. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb11445.x · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., Andrews-Hanna, J. R., Sperling, R. A., & Johnson, K. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5062-08.2009 · Cited by 2,862 · see citing works
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140 · see citing works
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265 · see citing works
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice
Lazarov, O., Robinson, J., Tang, Y.-P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M.-Y., Hersh, L. B., Sapolsky, R. M., Mirnics, K., & Sisodia, S. S. (2005) · Cell · doi:10.1016/j.cell.2005.01.015 · Cited by 885 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Jankowsky, J. L., Melnikova, T., Fadale, D. J., Xu, G. M., Slunt, H. H., Gonzales, V., Younkin, L. H., Younkin, S. G., Borchelt, D. R., & Savonenko, A. V. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5080-04.2005 · Cited by 517 · see citing works
Rice, H. C., de Malmazet, D., Schreurs, A., Frere, S., Van Molle, I., Volkov, A. N., Creemers, E., Vertkin, I., Nys, J., Ranaivoson, F. M., et al. (2019) · Science · doi:10.1126/science.aao4827 · Cited by 281 · see citing works
Deshpande, A., Kawai, H., Metherate, R., Glabe, C. G., & Busciglio, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5980-08.2009 · Cited by 232 · see citing works
Beta‐amyloid deposition and the aging brain
Rodrigue, K. M., Kennedy, K. M., & Park, D. C. (2009) · Neuropsychology Review · doi:10.1007/s11065-009-9118-x · Cited by 230 · see citing works
Lifespan brain activity, β-amyloid, and Alzheimer's disease
Jagust, W. J., & Mormino, E. C. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.09.004 · Cited by 221 · see citing works
Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion
Nitsch, R. M., Deng, M., Growdon, J. H., & Wurtman, R. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4188 · Cited by 219 · see citing works
Self-citationIn vivo characterization of the early states of the amyloid-beta network
Sepulcre, J., Sabuncu, M. R., Becker, A., Sperling, R., & Johnson, K. A. (2013) · Brain · doi:10.1093/brain/awt146 · Cited by 117 · see citing works
Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
Leal, S. L., Landau, S. M., Bell, R. K., & Jagust, W. J. (2017) · eLife · doi:10.7554/elife.22978 · Cited by 117 · see citing works
The keystone of Alzheimer pathogenesis might be sought in Aβ physiology
Puzzo, D., Gulisano, W., Arancio, O., & Palmeri, A. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.039 · Cited by 116 · see citing works
Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells
Brunholz, S., Sisodia, S., Lorenzo, A., Deyts, C., Kins, S., & Morfini, G. (2012) · Experimental Brain Research · doi:10.1007/s00221-011-2870-1 · Cited by 92 · see citing works
Lloret, M.-A., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D., & Lloret, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031168 · Cited by 68 · see citing works
Eggert, S., Kins, S., Endres, K., & Brigadski, T. (2022) · Biological Chemistry · doi:10.1515/hsz-2021-0330 · Cited by 46 · see citing works
Age as Risk Factor for Sporadic Dementia of the Alzheimer Type?
HOYER, S. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb56833.x · Cited by 38 · see citing works
- Authors
- Nitsch, R. M., Farber, S. A., Growdon, J. H., & Wurtman, R. J.
- Affiliations
- Massachusetts Institute of Technology (US)
- ORCID
- Farber, S A
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-06
- Volume
- 90
- Issue
- 11
- Pages
- 5191-5193
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC46681
- OpenAlex
- W2046948924
- Cited by
- 244
- References
- 20
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 9 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid precursor protein, APP processing, hippocampal slices, neurotransmitter release, tetrodotoxin, sodium channels, action potential, neuronal activity regulation, cerebrospinal fluid, lactate dehydrogenase
- MeSH terms
- Acetylcholine, Animals, Electric Stimulation, Hippocampus, L-Lactate Dehydrogenase, Male, Perfusion, Tetrodotoxin, Immunoblotting, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Rats, In Vitro Techniques
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