Increased intraneuronal resting [Ca2+] in adult Alzheimer’s disease mice
Abstract
Neurodegeneration in Alzheimer’s disease (AD) has been linked to intracellular accumulation of misfolded proteins and dysregulation of intracellular Ca 2+. In the current work, we determined the contribution of specific Ca 2+ pathways to an alteration in Ca 2+ homeostasis in primary cortical neurons from an adult triple transgenic (3xTg‐AD) mouse model of AD that exhibits intraneuronal accumulation of β‐amyloid proteins. Resting free Ca 2+ concentration ([Ca 2+]i), as measured with Ca 2+‐selective microelectrodes, was greatly elevated in neurons from 3xTg‐AD and APP SWE mouse strains when compared with their respective non‐transgenic neurons, while there was no alteration in the resting membrane potential. In the absence of the extracellular Ca 2+, the [Ca 2+]i returned to near normal levels in 3xTg‐AD neurons, demonstrating that extracellular Ca 2+contributed to elevated [Ca 2+]i. Application of nifedipine, or a non‐L‐type channel blocker, SKF‐96365, partially reduced [Ca 2+]i. Blocking the ryanodine receptors, with ryanodine or FLA‐365 had no effect, suggesting that these channels do not contribute to the elevated [Ca 2+]i. Conversely, inhibition of inositol trisphosphate receptors with xestospongin C produced a partial reduction in [Ca 2+]i. These results demonstrate that an elevation in resting [Ca 2+]i, contributed by aberrant Ca 2+entry and release pathways, should be considered a major component of the abnormal Ca 2+ homeostasis associated with AD.
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Application of Aβ to hippocampal slices elevates resting Ca2+ levels.
“application of Aβ to hippocampal slices elevates resting Ca2+ levels [52, 53].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [52]
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“This has been shown in AD mouse models, particularly in the area surrounding amyloid plaques, and application of Aβ to hippocampal slices elevates resting Ca2+ levels [52, 53].”
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- Authors
- Lopez, J. R., Lyckman, A., Oddo, S., LaFerla, F. M., Querfurth, H. W., & Shtifman, A.
- Affiliations
- Tufts University (US)
- University of California, Irvine (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-11-16
- Volume
- 105
- Issue
- 1
- Pages
- 262-271
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2041727630
- Cited by
- 162
- References
- 60
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 17 · 2021: 4 · 2020: 16 · 2019: 9 · 2018: 14 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 7 · 2012: 14
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01 AR46513, 1P01 AR52354, R01AR046513, P01AR052354)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- Alzheimer's disease, calcium homeostasis, 3xTg-AD mice, cortical neurons, extracellular calcium, L-type calcium channels, IP3 receptor, ryanodine receptor, amyloid-beta, neurodegeneration, xestospongin C, nifedipine
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Calcium, Calcium Channel Blockers, Cells, Cultured, Disease Models, Animal, Homeostasis, Humans, Mice, Transgenic, Neurons, Ryanodine, Amyloid beta-Protein Precursor, tau Proteins, Neocortex, Calcium Signaling, Calcium Channels, L-Type, Mice, Presenilin-1
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