ArticleJournal of neuroinflammation2021
Astrocytic C-X-C motif chemokine ligand-1 mediates β-amyloid-induced synaptotoxicity.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
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- Primary cortical cell tri-culture to study effects of amyloid-β on microglia function and neuroinflammatory response.Journal of Alzheimer's disease : JAD · 2024Article
- iPSC-derived PSEN2 (N141I) astrocytes and microglia exhibit a primed inflammatory phenotype.Journal of neuroinflammation · 2024Article
- P2XBrain, behavior, and immunity · 2023Article
- As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Amyloid-β Pathology-Specific Cytokine Secretion Suppresses Neuronal Mitochondrial Metabolism.Cellular and molecular bioengineering · 2023Article
- Proteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric Aβ.Journal of neurochemistry · 2023Article
- Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.International journal of molecular sciences · 2023Article
- Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Astrocytes in Neurodegeneration: Inspiration From Genetics.Frontiers in neuroscience · 2022Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPathological interactions between β-amyloid (Aβ) and tau drive synapse loss and cognitive decline in Alzheimer's disease (AD). Reactive astrocytes, displaying altered functions, are also a prominent feature of AD brain. This large and heterogeneous population of cells are increasingly recognised as contributing to early phases of disease. However, the contribution of astrocytes to Aβ-induced synaptotoxicity in AD is not well understood.
methodsWe stimulated mouse and human astrocytes with conditioned medium containing concentrations and species of human Aβ that mimic those in human AD brain. Medium from stimulated astrocytes was collected and immunodepleted of Aβ before being added to naïve rodent or human neuron cultures. A cytokine, identified in unbiased screens of stimulated astrocyte media and in postmortem human AD brain lysates was also applied to neurons, including those pre-treated with a chemokine receptor antagonist. Tau mislocalisation, synaptic markers and dendritic spine numbers were measured in cultured neurons and organotypic brain slice cultures.
resultsWe found that conditioned medium from stimulated astrocytes induces exaggerated synaptotoxicity that is recapitulated following spiking of neuron culture medium with recombinant C-X-C motif chemokine ligand-1 (CXCL1), a chemokine upregulated in AD brain. Antagonism of neuronal C-X-C motif chemokine receptor 2 (CXCR2) prevented synaptotoxicity in response to CXCL1 and Aβ-stimulated astrocyte secretions.
conclusionsOur data indicate that astrocytes exacerbate the synaptotoxic effects of Aβ via interactions of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting this chemokine-receptor pair as a novel target for therapeutic intervention 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.