Cited by 162Alzheimer's disease research and treatmentsCalcium signaling and nucleotide metabolismIon channel regulation and function

Increased intraneuronal resting [Ca2+] in adult Alzheimer’s disease mice

Lopez, José R., Lyckman, Alvin, Oddo, Salvatore, LaFerla, Frank M., Querfurth, Henry W., Shtifman, Alexander·2008·Journal of Neurochemistry

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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Crossref · 10.1111/j.1471-4159.2007.05135.x

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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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