ArticleBrain, behavior, and immunity2014
Age-dependent changes on TGFβ1 Smad3 pathway modify the pattern of microglial cell activation.
Article in Brain, behavior, and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 106 citations in OpenAlex.
- Treg-microglia crosstalk in Alzheimer's disease: stage-dependent dynamics, molecular mechanisms, and translational challenge.Frontiers in aging neuroscience · 2026Review
- Microglial Deletion of Hrh4 Alleviates Alzheimer's Disease Pathologies by Enhancing Microglial Phagocytosis of Amyloid-β and Tau.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Age-Related Changes in Neuron-Microglia Interaction Mediated by Fractalkine Under Inflammatory Conditions.International journal of molecular sciences · 2025Article
- 18 kDa TSPO targeting drives polarized human microglia towards a protective and restorative neurosteroidome profile.Cellular and molecular life sciences : CMLS · 2025Article
- Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.Advances in experimental medicine and biology · 2025Review
- Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model.Frontiers in physiology · 2024Article
- Aging Microglia and Their Impact in the Nervous System.Advances in neurobiology · 2024Review
- Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders.Neurochemical research · 2023Article
- An aging, pathology burden, and glial senescence build-up hypothesis for late onset Alzheimer's disease.Nature communications · 2023Review
- TGF-β1 signalling in Alzheimer's pathology and cytoskeletal reorganization: a specialized Tau perspective.Journal of neuroinflammation · 2023Review
- Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression.Frontiers in immunology · 2023Review
- Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- Article
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- TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications.Biomedicines · 2022Review
- Recent Advances in Microglia Modelling to Address Translational Outcomes in Neurodegenerative Diseases.Cells · 2022Review
- Microbiota-microglia connections in age-related cognition decline.Aging cell · 2022Review
- Microglia regulation of synaptic plasticity and learning and memory.Neural regeneration research · 2022Review
- Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection.Molecules (Basel, Switzerland) · 2022Review
- Intracerebral Hemorrhage: The Effects of Aging on Brain Injury.Frontiers in aging neuroscience · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aging is the main risk factor for Alzheimer's disease. Among other characteristics, it shows changes in inflammatory signaling that could affect the regulation of glial cell activation. We have shown that astrocytes prevent microglial cell cytotoxicity by mechanisms mediated by TGFβ1. However, whereas TGFβ1 is increased, glial cell activation persists in aging. To understand this apparent contradiction, we studied TGFβ1-Smad3 signaling during aging and their effect on microglial cell function. TGFβ1 induction and activation of Smad3 signaling in the hippocampus by inflammatory stimulation was greatly reduced in adult mice. We evaluated the effect of TGFβ1-Smad3 pathway on the regulation of nitric oxide (NO) and reactive oxygen species (ROS) secretion, and phagocytosis of microglia from mice at different ages with and without in vivo treatment with lipopolysaccharide (LPS) to induce an inflammatory status. NO secretion was only induced on microglia from young mice exposed to LPS, and was potentiated by inflammatory preconditioning, whereas in adult mice the induction of ROS was predominant. TGFβ1 modulated induction of NO and ROS production in young and adult microglia, respectively. Modulation was partially dependent on Smad3 pathway and was impaired by inflammatory preconditioning. Phagocytosis was induced by inflammation and TGFβ1 only in microglia cultures from young mice. Induction by TGFβ1 was also prevented by Smad3 inhibition. Our findings suggest that activation of the TGFβ1-Smad3 pathway is impaired in aging. Age-related impairment of TGFβ1-Smad3 can reduce protective activation while facilitating cytotoxic activation of microglia, potentiating microglia-mediated neurodegeneration.
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