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Amyloid pathology‐produced unexpected modifications of calcium homeostasis in hippocampal subicular dendrites
Author(s) -
Angulo Sergio L.,
Henzi Thomas,
Neymotin Samuel A.,
Suarez Manuel D.,
Lytton William W.,
Schwaller Beat,
Moreno Herman
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.07.017
Subject(s) - subiculum , hippocampal formation , dentate gyrus , neuroscience , calbindin , hippocampus , calcium imaging , homeostasis , calcium , chemistry , endocrinology , medicine , biology , microbiology and biotechnology
Alzheimer's disease (AD) is linked to neuronal calcium dyshomeostasis, which is associated with network hyperexcitability. Decreased expression of the calcium‐binding protein cal‐ bindin‐D 28K (CB) might be a susceptibility factor for AD. The subiculum is affected early in AD, for unknown reasons. Methods In AD, CB knock‐out and control mice fluorescence Ca 2+ imaging combined with patch clamp were used to characterize Ca 2+ dynamics, resting Ca 2+ , and Ca 2+ ‐buffering capacity in subicular neurons. CB expression levels in wild‐type and AD mice were also analyzed. Results The subiculum and dentate gyrus of wild‐type mice showed age‐related decline in CB expression not observed in AD mice. Resting Ca 2+ and Ca 2+ ‐buffering capacity was increased in aged AD mice subicular dendrites. Modeling suggests that AD calcium changes can be explained by alterations of Ca 2+ extrusion pumps rather than by buffers. Discussion Overall, abnormal Ca 2+ homeostasis in AD has an age dependency that comprises multiple mechanisms, including compensatory processes.