ArticleMolecular psychiatry2022
Microglia and their LAG3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive stimulation.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Contemporary in vivo rodent electroconvulsive therapy (ECT) models in translational depression research: a systematic review.Translational psychiatry · 2025Pooled it
- Histone H3K18 Lactylation Contributes to Perioperative Neurocognitive Disorder Through Immune Checkpoint Lymphocyte Activation Gene 3 Mediated Microglial Pyroptosis.CNS neuroscience & therapeutics · 2026Article
- Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice.Journal of neuroinflammation · 2026Article
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- Electroacupuncture promotes BDNF-dependent neurogenesis via microglial reprogramming in a chronic stress model.Chinese medicine · 2026Article
- Microglial Lag3 Drives α-Synuclein-induced Neurotoxic Activated (A1) Astrocytes and Neurodegeneration.bioRxiv : the preprint server for biology · 2026Article
- The postictal systems window hypothesis of electroconvulsive therapy in major depression.Frontiers in psychiatry · 2026Article
- Defining functional states and roles of microglia in neuropsychiatric disorders.Frontiers in cellular neuroscience · 2026Review
- Activated microglial exosomes enhance α-Synuclein internalization and accelerate neurodegeneration in lewy body dementia.Journal of nanobiotechnology · 2025Article
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- Rodent chronic variable stress procedures: A disjunction between stress entity and impact on behaviour.Journal of neuroendocrinology · 2025Review
- Propofol Modulates Microglial Glucose Metabolism Via the AMPK/HIF-1α Signaling Pathway To Ameliorate ECS-induced Cognitive Deficits in Depressive-like Rats.Neurochemical research · 2025Article
- EGR2 maintains neuropathic pain by promoting microglial phagocytosis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Microglia Sing the Prelude of Neuroinflammation-Associated Depression.Molecular neurobiology · 2025Review
- Identification of Novel Mosaic Variants in Focal Epilepsy-Associated Patients' Brain Lesions.Genes · 2025Article
- Glia as a New Target for Therapeutic Actions of Electroconvulsive Therapy.CNS & neurological disorders drug targets · 2025Review
- Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Engagement ofActa pharmaceutica Sinica. B · 2024Article
- Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy.BMC psychiatry · 2024Article
- Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?Current neuropharmacology · 2024Article
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite evidence implicating microglia in the etiology and pathophysiology of major depression, there is paucity of information regarding the contribution of microglia-dependent molecular pathways to antidepressant procedures. In this study, we investigated the role of microglia in a mouse model of depression (chronic unpredictable stress-CUS) and its reversal by electroconvulsive stimulation (ECS), by examining the effects of microglia depletion with the colony stimulating factor-1 antagonist PLX5622. Microglia depletion did not change basal behavioral measures or the responsiveness to CUS, but it completely abrogated the therapeutic effects of ECS on depressive-like behavior and neurogenesis impairment. Treatment with the microglia inhibitor minocycline concurrently with ECS also diminished the antidepressant and pro-neurogenesis effects of ECS. Hippocampal RNA-Seq analysis revealed that ECS significantly increased the expression of genes related to neurogenesis and dopamine signaling, while reducing the expression of several immune checkpoint genes, particularly lymphocyte-activating gene-3 (Lag3), which was the only microglial transcript significantly altered by ECS. None of these molecular changes occurred in microglia-depleted mice. Immunohistochemical analyses showed that ECS reversed the CUS-induced changes in microglial morphology and elevation in microglial LAG3 receptor expression. Consistently, either acute or chronic systemic administration of a LAG3 monoclonal antibody, which readily penetrated into the brain parenchyma and was found to serve as a direct checkpoint blocker in BV2 microglia cultures, rapidly rescued the CUS-induced microglial alterations, depressive-like symptoms, and neurogenesis impairment. These findings suggest that brain microglial LAG3 represents a promising target for novel antidepressant therapeutics.
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