Evidence map›Paper›PMID 33164928›Full record

ArticleJournal of Alzheimer's disease : JAD2020

Electrophysiological and Imaging Calcium Biomarkers of Aging in Male and Female 5×FAD Mice.

Adam O Ghoweri, Lara Ouillette, Hilaree N Frazier, Katie L Anderson, Ruei-Lung Lin, John C Gant, Rachel Parent, Shannon Moore, Geoffrey G Murphy, Olivier Thibault

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Adam O GhoweriUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Lara Ouillette5037 BSRB, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Hilaree N FrazierUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Katie L AndersonUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Ruei-Lung LinUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
John C GantUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Rachel Parent5037 BSRB, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Shannon Moore5037 BSRB, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Geoffrey G Murphy5037 BSRB, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Olivier ThibaultUKMC MS313, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.

Funding

Novel Imaging Biomarker for Treating Spatial Memory Loss in Prodromal Alzheimer's Disease ModelsR01AG058171 · NIA · WAYNE STATE UNIVERSITY · PI BENNETT, BRIAN M, BERKOWITZ, BRUCE A. · 2017 to 2021
$2.8M
Training in Translational Research in Alzheimer's and Related Dementias (TRIAD)T32AG057461 · NIA · UNIVERSITY OF KENTUCKY · PI MURPHY, MICHAEL PAUL, VAN ELDIK, LINDA J · 2017 to 2021
$2.1M
Testing the Calcium Hypothesis of Age-related Cognitive DeclineR01AG052934 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MURPHY, GEOFFREY G · 2016 to 2020
$2.1M
NIA NIH HHS R01 AG052934NIA NIH HHS R01 AG058171NIA NIH HHS T32 AG057461
6 · The paper itself

Abstract

backgroundIn animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer's disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker.

objectiveHere, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on a C57BL/6 genetic background using sharp electrodes coupled with Oregon-green Bapta-1 imaging. We focused on three ages that coincide with the course of amyloid deposition: 1.5, 4, and 10 months old.

methodsOutcome variables included measures of the afterhyperpolarization, short-term synaptic plasticity, and calcium kinetics during synaptic activation. Quantitative analyses of spatial learning and memory were also conducted using the Morris water maze. Main effects of sex, age, and genotype were identified on measures of electrophysiology and calcium imaging.

resultsMeasures of resting Oregon-green Bapta-1 fluorescence showed significant reductions in the 5×FAD group compared to controls. Deficits in spatial memory, along with increases in Aβ load, were detectable at older ages, allowing us to test for temporal associations with the onset of calcium dysregulation.

conclusionOur results provide evidence that reduced, rather than elevated, neuronal calcium is identified in this 5×FAD model and suggests that this surprising result may be a novel biomarker of AD.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCalciumFemaleHippocampusHumansMaleMiceMice, TransgenicMorris Water Maze TestNeuronal PlasticityNeuronsOptical ImagingPatch-Clamp TechniquesAmyloid beta-Protein PrecursorCalciumPresenilin-1PSEN1 protein, human5×FADafterhyperpolarizationagingAlzheimer’s diseasecalciumelectrophysiologyhippocampushyperactivityintracellularsex

Identifiers

PMID33164928
PMCPMC7836067

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.