ArticleJournal of advanced research2026
Deficit of neuronal EAAT2 impairs hippocampus CA3 neuron's activity and may induce depressive like behaviors.
Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Dihydromyricetin attenuates chronic stress-induced depressive-like phenotypes and modulates Akt/FoxO3a-related signaling in the hippocampus.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Network Pharmacology and Experimental Validation Reveal the Potential Antidepressant-Like Effects of Chaihu Shugan San Associated With Glutamate Homeostasis.Food science & nutrition · 2026Article
- Depression and Anxiety After Radiation-Induced Brain Injury: A Review of Current Research Progress.Current oncology (Toronto, Ont.) · 2025Review
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Authors and funding
5 authors.
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Abstract
introductionMajor depressive disorder (MDD) is a severe neuropsychiatric disease that is accompanied by hippocampal dysfunction. Currently, the complex neuronal types and molecules involved in the various hippocampal subfields in patients with depression remain unclear.
objectivesWe focused on the role of hippocampal excitatory amino acid transporter 2 (EAAT2) in chronic stress.
methodsWe studied two chronic stress models, the chronic unpredictable mild stress (CUMS) and the chronic social defeat stress (CSDS) models, and performed pharmacological inhibition, genetic manipulations to examine overexpression of neuron-specific solute carrier family 1 member 2 (SLC1A2), the gene encoding EAAT2, in the dorsal CA3 and conditional Slc1a2 knockout in CA3, whole-cell recording, and behavioral tests.
resultsOur results indicated that decreased EAAT2 expression and specific inhibition were associated with depression-like behavior and enhanced CA3 pyramidal neuron activity. In addition, neuron-specific EAAT2 overexpression in the CA3 yielded antidepressant-like effects and inhibited CA3 pyramidal neuron hyperactivity, whereas conditional CA3 EAAT2 knockout showed opposite effects at both behavioral and functional levels. We also found that the single-nucleotide polymorphism, rs77619780, in the SLCA1A2 gene was associated with lower MDD risk.
conclusionOur findings revealed that EAAT2 deficit in the CA3 induces depression-like behavior, which offers novel insight into MDD pathophysiology.
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