ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer's disease.
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 176 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
176 citing papers in PubMed, 2 syntheses or guidelines pooled it, 304 citations in OpenAlex.
- Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration.Journal of neuroinflammation · 2020Pooled it
- From Proteinopathy to Immunopathy in Alzheimer's Disease-A Role for Astrocytic Calcineurin?Journal of neurochemistry · 2026Article
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Article
- Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.Nature reviews. Neuroscience · 2026Review
- Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Neuroinflammation in Alzheimer's disease: glial crosstalk, pathological modulation, and therapeutic implications.Frontiers in immunology · 2026Review
- A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice.Brain communications · 2026Article
- Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin.Molecular neurobiology · 2025Article
- The GLP1R Agonist Semaglutide Inhibits Reactive Astrocytes and Enhances the Efficacy of Neural Stem Cell Transplantation Therapy in Parkinson's Disease Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Electroacupuncture ameliorates cognitive dysfunction in T2DM rats by modulating astrocytic polarization and aberrant energy metabolism in the hippocampus via the Wnt/β-catenin pathway.Diabetology & metabolic syndrome · 2025Article
- Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet-Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Inhibition of astrocyte signaling leads to sex-specific changes in microglia phenotypes in a diet-based model of cerebral small vessel disease.Journal of neuroinflammation · 2025Article
- Astrovascular decoupling in awake 5×FAD mice is associated with reduced astrocytic calcium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Experimental modeling of Alzheimer's disease: Translational lessons from cross-taxon analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Celebrating 40 years of the University of Kentucky Alzheimer's Disease Research Center.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease.Neurobiology of aging · 2025Article
116 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
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes in APP/PS1 mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with the immune/inflammatory calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway, shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation. After several months of treatment with Gfa2-VIVIT, APP/PS1 mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies.
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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.