ArticleProceedings of the National Academy of Sciences of the United States of America2019
Divergent roles of astrocytic versus neuronal EAAT2 deficiency on cognition and overlap with aging and Alzheimer's molecular signatures.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review.Frontiers in neuroscience · 2022Pooled it
- Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.Brain : a journal of neurology · 2021Trial
- Functional and Transcriptional Downregulation of Glutamate Transporters (EAAT1 and EAAT2) via DNMT3B Overexpression in Glial Cells.Molecular neurobiology · 2026Article
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Astrocyte-Specific Upregulation of Tumor Necrosis Factor Receptor II Ameliorates Pathological Phenotypes in APPNeuroscience bulletin · 2026Article
- hiPSC-derived cortical neurons from ADHD individuals reveal dysregulated glutamatergic development.Molecular psychiatry · 2026Article
- Neurovascular unit remodeling: focusing on glial cells in stroke injury and recovery.Frontiers in cellular neuroscience · 2026Review
- NMDA receptor mediated tonic excitatory currents are elicited by EAAT inhibition on human neocortical pyramidal neurons.Frontiers in synaptic neuroscience · 2026Article
- Pigment Epithelium-Derived Factor Deficiency Impairs Hippocampal Glutamate Homeostasis and Cognitive Function by Downregulating Astrocytic GLT-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel modulator of the Axin/β-Catenin interaction to restore EAAT2 expression in alzheimer's disease: an in-silico and in-vitro approach.Metabolic brain disease · 2025Article
- Pericytes change function depending on glioblastoma vicinity: emphasis on immune regulation.Molecular oncology · 2025Article
- The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.Immunity · 2025Article
- Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia.Schizophrenia bulletin · 2025Article
- Crystallin Alpha B Inhibits Cocaine-Induced Conditioned Place Preference via the Modulation of Dopaminergic Neurotransmission.Addiction biology · 2025Article
- Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer's Disease.ACS pharmacology & translational science · 2025Review
- Enhancement of Glutamate Uptake as Novel Antiseizure Approach: Preclinical Proof of Concept.Annals of neurology · 2025Article
- Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT-1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production.Journal of neurochemistry · 2025Article
- Common and divergent pathways in early stages of glutamate and tau-mediated toxicities in neurodegeneration.Experimental neurology · 2024Article
- The Transcriptional Landscape of Pericytes in Acute Ischemic Stroke.Translational stroke research · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter in the brain expressed predominantly in astrocytes and at low levels in neurons and axonal terminals. EAAT2 expression is reduced in aging and sporadic Alzheimer's disease (AD) patients' brains. The role EAAT2 plays in cognitive aging and its associated mechanisms remains largely unknown. Here, we show that conditional deletion of astrocytic and neuronal EAAT2 results in age-related cognitive deficits. Astrocytic, but not neuronal EAAT2, deletion leads to early deficits in short-term memory and in spatial reference learning and long-term memory. Neuronal EAAT2 loss results in late-onset spatial reference long-term memory deficit. Neuronal EAAT2 deletion leads to dysregulation of the kynurenine pathway, and astrocytic EAAT2 deficiency results in dysfunction of innate and adaptive immune pathways, which correlate with cognitive decline. Astrocytic EAAT2 deficiency also shows transcriptomic overlaps with human aging and AD. Overall, the present study shows that in addition to the widely recognized astrocytic EAAT2, neuronal EAAT2 plays a role in hippocampus-dependent memory. Furthermore, the gene expression profiles associated with astrocytic and neuronal EAAT2 deletion are substantially different, with the former associated with inflammation and synaptic function similar to changes observed in human AD and gene expression changes associated with inflammation similar to the aging human brain.
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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.