Neurotoxicity of Aβ amyloid protein in vitro is not altered by calcium channel blockade
Abstract
In cortical cultures, A beta protein destabilizes calcium homeostasis, but direct neurotoxicity of A beta is not observed. In hippocampal cultures, we and others find treatment with A beta protein decreases neuronal survival, but the mechanism of neurotoxicity is unknown. We have used low-density, serum-free cultures of hippocampal neurons to determine whether the neurotoxicity of A beta protein in vitro can be altered by voltage- or ligand-gated calcium channel antagonists or cyclic nucleotides. In these cultures, neither omega-conotoxin, nifedipine, verapamil, APV, nor MK-801 altered the survival of neurons exposed to synthetic A beta 1-40. The N-channel antagonist diltiazem decreased A beta 1-40 toxicity repeatedly, but slightly, perhaps by indirectly contributing to increased neuronal viability. Treatment of cultures with dibutyryl cAMP, 8-bromo cAMP, dibutyryl cGMP, and 8-bromo cGMP also failed to alter A beta toxicity. Thus, the toxicity of beta protein in low-density hippocampal cultures was not directly altered either by calcium channel blockers or by the addition of cyclic nucleotides.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Results from recent studies assessing the impact of aging on hippocampal and other temporal lobe structures have been variable: some found age-related declines in volume in normal elderly individuals, while others did not.
“Results from recent studies assessing the impact of aging on hippocampal and other temporal lobe structures have been variable. Some have found age-related declines in volume in normal elderly individuals [4, 30, 31] while others have not [3, 32].”
From Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease (1998) · cites this paper as [32]
Cites
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619 · see citing works
Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
Yankner, B. A., Duffy, L. K., & Kirschner, D. A. (1990) · Science · doi:10.1126/science.2218531 · Cited by 1,975 · see citing works
Mattson, M. P., Cheng, B., Davis, D. G., Bryant, K., Lieberburg, I. M., & Rydel, R. E. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00376.1992 · Cited by 1,627 · see citing works
Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus
Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G. A. P., St George-Hyslop, P., Van Keuren, M. L., Patterson, D., Pagan, S., Kurnit, D. M., & Neve, R. L. (1987) · Science · doi:10.1126/science.2949367 · Cited by 1,611 · see citing works
Goldgaber, D., Lerman, M. I., McBride, O. W., Saffiotti, U., & Gajdusek, D. C. (1987) · Science · doi:10.1126/science.3810169 · Cited by 1,333 · see citing works
Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures
Dawson, V., Dawson, T., Bartley, D., Uhl, G. R., & Snyder, S. H. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-06-02651.1993 · Cited by 1,014 · see citing works
Arispe, N. J., Rojas, E., & Pollard, H. B. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.567 · Cited by 921 · see citing works
In vitro aging of ß-amyloid protein causes peptide aggregation and neurotoxicity
Pike, C. J., Walencewicz, A. J., Glabe, C. G., & Cotman, C. W. (1991) · Brain Research · doi:10.1016/0006-8993(91)91553-d · Cited by 829 · see citing works
β-Amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage
Koh, J., Yang, L. L., & Cotman, C. W. (1990) · Brain Research · doi:10.1016/0006-8993(90)91355-k · Cited by 617 · see citing works
Robakis, N. K. R. K., Ramakrishna, N., Wolfe, G. C., & Wisniewski, H. M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.12.4190 · Cited by 603 · see citing works
Amyloid β Protein Enhances the Survival of Hippocampal Neurons in Vitro
Whitson, J. S., Selkoe, D. J., & Cotman, C. W. (1989) · Science · doi:10.1126/science.2928783 · Cited by 469 · see citing works
Self-citationBrain glia release factors with opposing actions upon neuronal survival
Giulian, D., Vaca, K., & Corpuz, M. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-01-00029.1993 · Cited by 433 · see citing works
Zafra, F., Lindholm, D., Castren, E., Hartikka, J., & Thoenen, H. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-12-04793.1992 · Cited by 414 · see citing works
Mattson, M. P., Tomaselli, K. J., & Rydel, R. E. (1993) · Brain Research · doi:10.1016/0006-8993(93)90295-x · Cited by 379 · see citing works
Brewer, G. J., & Cotman, C. W. (1989) · Brain Research · doi:10.1016/0006-8993(89)90144-3 · Cited by 376 · see citing works
Giulian, D., Wendt, E., Vaca, K., & Noonan, C. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.7.2769 · Cited by 232 · see citing works
Down patients: Extracellular preamyloid deposits precede neuritic degeneration and senile plaques
Giaccone, G., Tagliavini, F., Linoli, G., Bouras, C., Frigerio, L., Frangione, B., & Bugiani, O. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90169-9 · Cited by 231 · see citing works
Methodological variables in the assessment of beta amyloid neurotoxicity
Busciglio, J. A., Lorenzo, A., & Yankner, B. A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90065-6 · Cited by 210 · see citing works
Weiss, J. H., Pike, C. J., & Cotman, C. W. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62010372.x · Cited by 210 · see citing works
β-Amyloid protein promotes neuritic branching in hippocampal cultures
Whitson, J. S., Glabe, C. G., Shintani, E., Abcar, A. C., & Cotman, C. W. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90867-9 · Cited by 185 · see citing works
Self-citationScholz, K. P., & Miller, R. J. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018900 · Cited by 177 · see citing works
Sahara, Y., & Westbrook, G. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-07-03041.1993 · Cited by 122 · see citing works
β-amyloid peptide in vitro toxicity: Lot-to-lot variability
May, P. C., Gitter, B. D., Waters, D. C., Simmons, L. K., Becker, G. W., Small, J. S., & Robison, P. M. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90064-5 · Cited by 116 · see citing works
Development of excitotoxicity in cultured hippocampal neurons
Peterson, C., Neal, J. H., & Cotman, C. W. (1989) · Developmental Brain Research · doi:10.1016/0165-3806(89)90075-8 · Cited by 104 · see citing works
Divergent effects of astroglial and microglial secretions on neuron growth and survival
Vaca, K., & Wendt, E. (1992) · Experimental Neurology · doi:10.1016/0014-4886(92)90023-j · Cited by 94 · see citing works
Tatsuno, I., Yada, T., Vígh, S., Hidaka, H., & Arimura, A. (1992) · Endocrinology · doi:10.1210/endo.131.1.1319331 · Cited by 91 · see citing works
Evidence of amyloid beta-protein immunoreactive early plaque lesions in Down's syndrome brains.
Ikeda, S., Yanagisawa, N., Allsop, D., & Glenner, G. G. (1989) · PubMed · Cited by 61 · see citing works
β-Amyloid precursor protein and alzheimer's disease: The peptide plot thickens
Mattson, M. P., & Rydel, R. E. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90068-9 · Cited by 59 · see citing works
Mangano, T. J., Patel, J. B., Salama, A. I., & Keith, R. A. (1991) · European Journal of Pharmacology · doi:10.1016/0014-2999(91)90062-u · Cited by 53 · see citing works
Ágoston, D. V., Eiden, L. E., Brenneman, D. E., & Gozes, I. (1991) · Molecular Brain Research · doi:10.1016/0169-328x(91)90066-7 · Cited by 44 · see citing works
Toselli, M., & Taglietti, V. (1992) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00374734 · Cited by 30 · see citing works
Marx, J. L. (1992) · Science · doi:10.1126/science.1529329 · Cited by 29 · see citing works
Modulation of acetylcholine release in rat hippocampus by amino alcohols and Bay K 8644
Bostwick, J. R., Abbe, R., & Appel, S. H. (1993) · Brain Research · doi:10.1016/0006-8993(93)90484-5 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Risk of Alzheimer's disease and duration of NSAID use
Stewart, W. F., Kawas, C., Corrada, M., & Metter, E. J. (1997) · Neurology · doi:10.1212/wnl.48.3.626 · Cited by 1,132 · see citing works
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease
Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., Smith, G. E., Ivnik, R. J., & Kokmen, E. (1997) · Neurology · doi:10.1212/wnl.49.3.786 · Cited by 1,128 · see citing works
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease
Jack, C. R., Petersen, R. C., Xu, Y., O'Brien, P. C., Smith, G. E., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1998) · Neurology · doi:10.1212/wnl.51.4.993 · Cited by 666 · see citing works
Amyloid β protein forms ion channels: implications for Alzheimer's disease pathophysiology
LIN, H., Bhatia, R., & Lal, R. (2001) · The FASEB Journal · doi:10.1096/fj.01-0377com · Cited by 641 · see citing works
Cummings, J. L., Vinters, H. V., Cole, G. M., & Khachaturian, Z. S. (1998) · Neurology · doi:10.1212/wnl.51.1_suppl_1.s2 · Cited by 515 · see citing works
Oxidative stress and β-amyloid protein in Alzheimer’s disease
Cai, Z., Zhao, B., & Ratka, A. (2011) · NeuroMolecular Medicine · doi:10.1007/s12017-011-8155-9 · Cited by 279 · see citing works
Alzheimer's disease: a re-examination of the amyloid hypothesis
Neve, R. L., & Robakis, N. K. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01168-5 · Cited by 261 · see citing works
Bhatia, R., Lin, H., & Lal, R. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.9.1233 · Cited by 224 · see citing works
Aβ ion channels. Prospects for treating Alzheimer's disease with Aβ channel blockers
Arispe, N. J., Díaz, J. C., & Šimáková, O. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.03.014 · Cited by 193 · see citing works
Brain volume preserved in healthy elderly through the eleventh decade
Mueller, E. A., Moore, M. M., Kerr, D., Sexton, G. J., Camicioli, R. M., Howieson, D. B., Quinn, J. F., & Kaye, J. A. (1998) · Neurology · doi:10.1212/wnl.51.6.1555 · Cited by 154 · see citing works
Ionic effects of the Alzheimer's disease β-amyloid precursor protein and its metabolic fragments
Fraser, S. P., Suh, Y.-H., & Djamgoz, M. B. A. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10079-5 · Cited by 123 · see citing works
Beta-amyloid peptide blocks the fast-inactivating K+ current in rat hippocampal neurons
Good, T. A., Smith, D. O., & Murphy, R. M. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79570-x · Cited by 120 · see citing works
The search for disease-modifying treatment for Alzheimer's disease
Aisen, P. S. S., & Davis, K. L. (1997) · Neurology · doi:10.1212/wnl.48.5_suppl_6.35s · Cited by 110 · see citing works
Ekinci, F. J., Linsley, M.-D., & Shea, T. B. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00025-5 · Cited by 106 · see citing works
Hiruma, H., Katakura, T., Takahashi, S., Ichikawa, T., & Kawakami, T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08967.2003 · Cited by 114 · see citing works
Harkany, T., Hortobágyi, T., Sasvári, M., Kónya, C., Penke, B., Luiten, P. G. M., & Nyakas, C. J. (1999) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(99)00058-5 · Cited by 97 · see citing works
Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity
Pollard, H. B., Arispe, N. J., & Rojas, E. (1995) · Cellular and Molecular Neurobiology · doi:10.1007/bf02071314 · Cited by 88 · see citing works
Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease
Payami, H., Schellenberg, G. D., Zareparsi, S., Kaye, J. A., Sexton, G. J., Head, M. A., Matsuyama, S. S., Jarvik, L. F., Miller, B. L., McManus, D. Q., et al. (1997) · Neurology · doi:10.1212/wnl.49.2.512 · Cited by 84 · see citing works
Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia
Katzman, R., Zhang, M.-Y., Chen, P. J., Gu, N., Jiang, S., Saitoh, T., Chen, X., Klauber, M. R., Thomas, R. G., Liu, W. T., et al. (1997) · Neurology · doi:10.1212/wnl.49.3.779 · Cited by 78 · see citing works
Madrigal, J. L. M., Kalinin, S., Richardson, J. C., & Feinstein, D. L. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04888.x · Cited by 77 · see citing works
Aβ(25–35) and Aβ(1–40) act on different calcium channels in CA1 hippocampal neurons
Rovira, C., Arbez, N., & Mariani, J. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02072-7 · Cited by 68 · see citing works
Kourie, J. I. (2001) · Cellular and Molecular Neurobiology · doi:10.1023/a:1010932603406 · Cited by 67 · see citing works
CSF tau is related to apolipoprotein E genotype in early Alzheimer's disease
Tapiola, T., Lehtovirta, M., Ramberg, J., Helisalmi, S., Linnaranta, K., Riekkinen, P., & Soininen, H. S. (1998) · Neurology · doi:10.1212/wnl.50.1.169 · Cited by 63 · see citing works
Huang, H., Ou, H., Hsieh, S., & Chiang, L.-Y. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00470-7 · Cited by 60 · see citing works
Jalonen, T. O., Charniga, C. J., & Wielt, D. B. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01189-4 · Cited by 59 · see citing works
Cataldi, M. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311030004 · Cited by 44 · see citing works
Nicotine and its interaction with β-amyloid protein: a short review
Zamani, R., & Allen, Y. S. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01108-2 · Cited by 42 · see citing works
Kourie, J. I. (2001) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(01)00228-9 · Cited by 40 · see citing works
Amyloid beta protein (25–35) stimulation of phospholipases A, C and D activities of LA‐N‐2 cells
Singh, I., McCartney, D., & Kanfer, J. N. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00432-9 · Cited by 39 · see citing works
Pourbadie, H. G., Naderi, N., Khodagholi, F., Shaerzadeh, F., & Motamedi, F. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.09.045 · Cited by 37 · see citing works
Verapamil and Alzheimer’s Disease: Past, Present, and Future
Popović, N., Morales-Delgado, N., Mena, D. V., Alonso, A., Martínez, M. P., Bleda, M. C., & Popović, M. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00562 · Cited by 33 · see citing works
Apoptosis in Neurodegenerative Diseases
Nishimoto, I., Okamoto, T., Giambarella, U., & Iwatsubo, T. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)61064-9 · Cited by 27 · see citing works
cAMP delays beta-amyloid (25-35) induced cell death in rat cortical neurons
Parvathenani, L. K., Calandra, V., Roberts, S. B., & Posmantur, R. M. (2000) · Neuroreport · doi:10.1097/00001756-200007140-00045 · Cited by 18 · see citing works
Glutamate Receptors in Aging and Alzheimer's Disease
Mishizen-Eberz, A. J., Ikonomović, M. D., & Armstrong, D. M. (2001) · Elsevier eBooks · doi:10.1016/b978-012351830-9/50022-6 · Cited by 15 · see citing works
Theoretical studies on Alzheimer's disease: structures of β-amyloid aggregates
Kim, S. T., & Weaver, D. F. (2000) · Journal of Molecular Structure THEOCHEM · doi:10.1016/s0166-1280(00)00485-1 · Cited by 9 · see citing works
Chapter 2. Alzheimer's Disease: Recent Advances on the Amyloid Hypothesis
John, V., Latimer, L. H., Tung, J. S., & Dappen, M. S. (1997) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)61460-8 · Cited by 6 · see citing works
Modeling the short time-scale dynamics of β-amyloid–neuron interactions
Wilson, N., Gates, B., & Castellanos, M. (2013) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2013.02.012 · Cited by 4 · see citing works
Chapter 7 Neuronal Aging and Alzheimer's Disease
Bosman, G. J. C. G. M., & Grip, W. J. D. (1996) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(08)60042-5 · Cited by 2 · see citing works
Cytotoxic properties of amyloidogenic L68Q cystatin C. A search for therapeutic agents
Ingólfsdóttir, I. E. (2013)
- Authors
- Whitson, J. S., & Appel, S. H.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Appel, S.H.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 16
- Issue
- 1
- Pages
- 5-10
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2037639183
- Cited by
- 41
- References
- 33
- Citations by year
- 2020: 1 · 2013: 3 · 2012: 1
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50ag008664-09)
- National Institute on Aging (AG00183, AG-08664)
- 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-beta, Aβ(1-40), neurotoxicity, calcium channel blockers, calcium homeostasis, hippocampal neurons, neuronal survival, diltiazem, omega-conotoxin, nifedipine, verapamil, APV, MK-801, cyclic nucleotides, Alzheimer's disease
- MeSH terms
- Cyclic AMP, Animals, Calcium Channel Blockers, Cell Survival, Cells, Cultured, Cyclic GMP, Hippocampus, Hydrolysis, Immunohistochemistry, Trypsin, Ion Channel Gating, Amyloid beta-Peptides, Tissue Fixation, Culture Media, Serum-Free, Rats, Sprague-Dawley, Rats
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