ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Early presynaptic and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer's disease mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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Who cites it
75 citing papers in PubMed, 117 citations in OpenAlex.
- Oral Exposure to Food-Grade Nanoparticles Poses a Risk of Alzheimer's Disease-Like Symptoms by Triggering Autophagy Defects in Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.Science (New York, N.Y.) · 2024Article
- Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Review
- Aß Pathology and Neuron-Glia Interactions: A Synaptocentric View.Neurochemical research · 2023Review
- Elevated amyloid beta disrupts the nanoscale organization and function of synaptic vesicle pools in hippocampal neurons.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Upregulated CaCells · 2022Article
- Mitochondria-Endoplasmic Reticulum Interplay Regulates Exo-Cytosis in Human Neuroblastoma Cells.Cells · 2022Article
- Inbred Mice Again at Stake: How the Cognitive Profile of the Wild-Type Mouse Background Discloses Pathogenic Effects of APP Mutations.Frontiers in behavioral neuroscience · 2022Review
- β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of CaCell reports · 2021Article
- Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.International journal of molecular sciences · 2021Review
- CaCells · 2020Review
- SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Alterations of the Endoplasmic Reticulum (ER) Calcium Signaling Molecular Components in Alzheimer's Disease.Cells · 2020Review
- Limiting RyR2 Open Time Prevents Alzheimer's Disease-Related Neuronal Hyperactivity and Memory Loss but Not β-Amyloid Accumulation.Cell reports · 2020Article
- Neural compensation in presymptomatic hAPP mouse models of Alzheimer's disease.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD)-linked presenilin (PS) mutations result in pronounced endoplasmic reticulum calcium disruptions that occur before detectable histopathology and cognitive deficits. More subtly, these early AD-linked calcium alterations also reset neurophysiological homeostasis, such that calcium-dependent presynaptic and postsynaptic signaling appear functionally normal yet are actually operating under aberrant calcium signaling systems. In these 3xTg-AD mouse brains, upregulated ryanodine receptor (RyR) activity is associated with a shift toward synaptic depression, likely through a reduction in presynaptic vesicle stores and increased postsynaptic outward currents through small-conductance calcium-activated potassium SK2 channels. The deviant RyR-calcium involvement in the 3xTg-AD mice also compensates for an intrinsic predisposition for hippocampal long-term depression (LTD) and reduced long-term potentiation (LTP). In this study, we detail the impact of disrupted RyR-mediated calcium stores on synaptic transmission properties, LTD, and calcium-activated membrane channels of hippocampal CA1 pyramidal neurons in presymptomatic 3xTg-AD mice. Using electrophysiological recordings in young 3xTg-AD and nontransgenic (NonTg) hippocampal slices, we show that increased RyR-evoked calcium release in 3xTg-AD mice "normalizes" an altered synaptic transmission system operating under a shifted homeostatic state that is not present in NonTg mice. In the process, we uncover compensatory signaling mechanisms recruited early in the disease process that counterbalance the disrupted RyR-calcium dynamics, namely increases in presynaptic spontaneous vesicle release, altered probability of vesicle release, and upregulated postsynaptic SK channel activity. Because AD is increasingly recognized as a "synaptic disease," calcium-mediated signaling alterations may serve as a proximal trigger for the synaptic degradation driving the cognitive loss in AD.
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Registered trials
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.