ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Cross Talk Between Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer's Amyloid-β Oligomers in Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer's disease: a systematic review of symptom-general and -specific lesion patterns.Molecular neurodegeneration · 2021Pooled it
- Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms.Molecules (Basel, Switzerland) · 2018Pooled it
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.Psychopharmacology · 2020Trial
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Innate Immune Tolerance Regulates Microglia Response to Aβ Oligomers.Journal of neurochemistry · 2026Article
- Antiviral and immunomodulatory effects of Chaihu Guizhi decoction in an acute depression-like mouse model infected with influenza A virus.Animal models and experimental medicine · 2025Article
- Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways.International journal of molecular sciences · 2025Article
- Neonatal maternal separation causes depressive-like behavior and potentiates memory impairment induced by amyloid-β oligomers in adult mice.Behavioral and brain functions : BBF · 2025Article
- Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Review
- The role of regulatory T cells in central nervous system diseases in dogs: fighting with a double-edged sword toward translational discoveries.American journal of translational research · 2025Review
- Premenstrual dysphoric disorder as a potential predisposing factor for Alzheimer's disease: a review.Frontiers in endocrinology · 2025Review
- Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Pathogenesis of Depression in Alzheimer's Disease.Neurochemical research · 2024Review
- The neural basis of neuropsychiatric symptoms in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Licochalcone A: A Potential Multitarget Drug for Alzheimer's Disease Treatment.International journal of molecular sciences · 2023Review
- Article
- Global trends and prospects about synaptic plasticity in Alzheimer's disease: a bibliometric analysis.Frontiers in aging neuroscience · 2023Review
- AVE 0991 Suppresses Astrocyte-Mediated Neuroinflammation of Alzheimer's Disease by Enhancing Autophagy.Journal of inflammation research · 2023Article
- Lung inflammation induced by silica particles triggers hippocampal inflammation, synapse damage and memory impairment in mice.Journal of neuroinflammation · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-α and abolished depressive-like behavior induced by AβOs. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, AβOs failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that AβOs trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia in the world. Brain accumulation of amyloid-β oligomers (AβOs) is a major feature in the pathogenesis of AD. Although clinical and epidemiological data suggest a strong connection between AD and depression, the underlying mechanisms linking these two disorders remain largely unknown. Here, we report that aberrant activation of the brain innate immunity and decreased serotonergic tonus in the brain are key players in AβO-induced depressive-like behavior in mice. Our findings may open up new possibilities for the development of effective therapeutics for AD and depression aimed at modulating microglial function.
Indexed as
Identifiers
What OpenQuestion holds
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.