ArticleNeuropathology and applied neurobiology2022
Extracellular tau oligomers affect extracellular glutamate handling by astrocytes through downregulation of GLT-1 expression and impairment of NKA1A2 function.
Article in Neuropathology and applied neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07732933 (GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder), which is not on this map. Cited by 17 papers.
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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.
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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.
GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder
Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
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- Emerging roles of astrocytes in hippocampal circuitry and behavior.Frontiers in cellular neuroscience · 2025Review
- Functional deletion of α7 nicotinic acetylcholine receptor impairs CaFrontiers in physiology · 2025Article
- Mechanisms of glutamate metabolic function and dysfunction in vascular dementia.Neuroprotection (Chichester, England) · 2024Review
- Brain clearance of protein aggregates: a close-up on astrocytes.Molecular neurodegeneration · 2024Review
- Tau and Amyloid β Protein in Patient-Derived Aqueous Brain Extracts Act Concomitantly to Disrupt Long-Term PotentiationThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Intracellular accumulation of tau oligomers in astrocytes and their synaptotoxic action rely on Amyloid Precursor Protein Intracellular Domain-dependent expression of Glypican-4.Progress in neurobiology · 2023Article
- Interleukin 1β triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex.Cellular and molecular life sciences : CMLS · 2023Article
- A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases.Journal of medicinal chemistry · 2023Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsSeveral studies reported that astrocytes support neuronal communication by the release of gliotransmitters, including ATP and glutamate. Astrocytes also play a fundamental role in buffering extracellular glutamate in the synaptic cleft, thus limiting the risk of excitotoxicity in neurons. We previously demonstrated that extracellular tau oligomers (ex-oTau), by specifically targeting astrocytes, affect glutamate-dependent synaptic transmission via a reduction in gliotransmitter release. The aim of this work was to determine if ex-oTau also impair the ability of astrocytes to uptake extracellular glutamate, thus further contributing to ex-oTau-dependent neuronal dysfunction.
methodsPrimary cultures of astrocytes and organotypic brain slices were exposed to ex-oTau (200 nM) for 1 h. Extracellular glutamate buffering by astrocytes was studied by: Na
resultsEx-oTau uploading in astrocytes significantly affected glutamate-transporter-1 expression and function, thus impinging on glutamate buffering activity. Ex-oTau also reduced Na-K-ATPase activity because of pump mislocalisation on the plasma membrane, with no significant changes in expression. This effect was independent of oTau internalisation and it caused Na
conclusionsEx-oTau exerted a complex action on astrocytes, at both intracellular and extracellular levels. The net effect was dysregulated glutamate signalling in terms of both release and uptake that relied on reduced expression of glutamate-transporter-1, altered function and localisation of NKA1A1, and NKA1A2. Consequently, Na
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