ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer's disease mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 85 citations in OpenAlex.
- The default mode network exhibits circuit-specific selective vulnerability despite widespread amyloid burden in an animal model of Alzheimer's disease.Nature communications · 2026Article
- Recent Advances in the ESIPT-based Responsive Probes for the Detection of Bio-Active Molecules CO, NO and H₂S.Journal of fluorescence · 2026Review
- Low-Intensity Focused Ultrasound Alters Alzheimer's Disease Pathology, In Vivo, as a Function of Ultrasound Dose and Age.Brain sciences · 2026Article
- Dantrolene normalizes heightened CaCell calcium · 2025Article
- An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.Molecular neurobiology · 2025Review
- Positive Allosteric Modulators of SERCA Pump Restore Dendritic Spines and Rescue Long-Term Potentiation Defects in Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2023Article
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- The Interplay between cGMP and Calcium Signaling in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Psychosis beas a rare side effect of sildenafil: a case report.Journal of medical case reports · 2022Article
- Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.European review for medical and pharmacological sciences · 2022Review
- 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
- Amyloid-β: a potential link between epilepsy and cognitive decline.Nature reviews. Neurology · 2021Review
- Sustained Hippocampal Synaptic Pathophysiology Following Single and Repeated Closed-Head Concussive Impacts.Frontiers in cellular neuroscience · 2021Article
- CaCells · 2020Review
- Safflower Yellow Improves Synaptic Plasticity in APP/PS1 Mice by Regulating Microglia Activation Phenotypes and BDNF/TrkB/ERK Signaling Pathway.Neuromolecular medicine · 2020Article
- Neural compensation in presymptomatic hAPP mouse models of Alzheimer's disease.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Development of novel phosphodiesterase 5 inhibitors for the therapy of Alzheimer's disease.Biochemical pharmacology · 2020Review
- Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease.Anesthesiology · 2020Article
- Electrophysiological and Imaging Calcium Biomarkers of Aging in Male and Female 5×FAD Mice.Journal of Alzheimer's disease : JAD · 2020Article
- Nitrosative Stress in the Frontal Cortex From Dogs With Canine Cognitive Dysfunction.Frontiers in veterinary science · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptic plasticity deficits are increasingly recognized as causing the memory impairments which define Alzheimer's disease (AD). In AD mouse models, evidence of abnormal synaptic function is present before the onset of cognitive deficits, and presents as increased synaptic depression revealed only when synaptic homeostasis is challenged, such as with suppression of ryanodine receptor (RyR)-evoked calcium signaling. Otherwise, at early disease stages, the synaptic physiology phenotype appears normal. This suggests compensatory mechanisms are recruited to maintain a functionally normal net output of the hippocampal circuit. A candidate calcium-regulated synaptic modulator is nitric oxide (NO), which acts presynaptically to boost vesicle release and glutamatergic transmission. Here we tested whether there is a feedforward cycle between the increased RyR calcium release seen in presymptomatic AD mice and aberrant NO signaling which augments synaptic plasticity. Using a combination of electrophysiological approaches, two-photon calcium imaging, and protein biochemistry in hippocampal tissue from presymptomatic 3xTg-AD and NonTg mice, we show that blocking NO synthesis results in markedly augmented synaptic depression mediated through presynaptic mechanisms in 3xTg-AD mice. Additionally, blocking NO reduces the augmented synaptically evoked dendritic calcium release mediated by enhanced RyR calcium release. This is accompanied by increased nNOS levels in the AD mice and is reversed upon normalization of RyR-evoked calcium release with chronic dantrolene treatment. Thus, recruitment of NO is serving a compensatory role to boost synaptic transmission and plasticity during early AD stages. However, NO's dual role in neuroprotection and neurodegeneration may convert to maladaptive functions as the disease progresses.
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