ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2012
Clozapine protects dopaminergic neurons from inflammation-induced damage by inhibiting microglial overactivation.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis.Schizophrenia bulletin · 2026Pooled it
- Greater Choline-Containing Compounds and Myo-inositol in Treatment-Resistant Versus Responsive Schizophrenia: ABiological psychiatry. Cognitive neuroscience and neuroimaging · 2024Pooled it
- Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis.Psychological medicine · 2021Pooled it
- Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update.Schizophrenia bulletin · 2014Pooled it
- Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and symptoms in schizophrenia.Brain imaging and behavior · 2021Trial
- Steroidomic Differences Among Clozapine, Olanzapine, and Risperidone in Male Patients with First-Episode Psychosis, Including a Treatment-Resistant Schizophrenia Subgroup.International journal of molecular sciences · 2026Article
- Clozapine Mitigates Lipopolysaccharide-Induced Cognitive Dysfunction by Modulating Cholinergic Function, Oxidative Stress, and Apoptotic Signaling in Rats.Life (Basel, Switzerland) · 2026Article
- Apolipoprotein D Expression Dynamics During Cuprizone-Induced Demyelination and Remyelination in a Mouse Model of Multiple Sclerosis.International journal of molecular sciences · 2025Article
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- The Role of Microglial Exosomes in Clozapine Treatment: Effect on Cognition in Schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Influence of antipsychotic drugs on microglia-mediated neuroinflammation in schizophrenia: perspectives in an astrocyte-microglia co-culture model.Frontiers in psychiatry · 2025Review
- COVID-19 disease outcomes in patients receiving clozapine versus other antipsychotics: a national study in Qatar.Frontiers in psychiatry · 2025Article
- Is treatment-resistant schizophrenia a neuroimmune condition? Meta-analytic evidence from magnetic resonance spectroscopy.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Clozapine suppresses NADPH oxidase activation, counteracts cytosolic HRedox biology · 2023Article
- Clozapine Suppresses the Gene Expression and the Production of Cytokines and Up-Regulates Cyclooxygenase 2 mRNA in Human Astroglial Cells.Brain sciences · 2022Article
- Psychedelic-inspired approaches for treating neurodegenerative disorders.Journal of neurochemistry · 2022Review
- The role of hypothalamic endoplasmic reticulum stress in schizophrenia and antipsychotic-induced weight gain: A narrative review.Frontiers in neuroscience · 2022Review
- Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.Molecular psychiatry · 2021Article
- Physiological Concentration of HCellular and molecular neurobiology · 2021Article
- Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study.Schizophrenia bulletin open · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Increasing evidence suggests a possible involvement of neuroinflammation in some psychiatric disorders, and also pharmacological reports indicate that anti-inflammatory effects are associated with therapeutic actions of psychoactive drugs, such as anti-depressants and antipsychotics. The purpose of this study was to explore whether clozapine, a widely used antipsychotic drugs, displays anti-inflammatory and neuroprotective effects. Using primary cortical and mesencephalic neuron-glia cultures, we found that clozapine was protective against inflammation-related neurodegeneration induced by lipopolysaccharide (LPS). Pretreatment of cortical or mesencephalic neuron-glia cultures with clozapine (0.1 or 1 μM) for 24 h attenuated LPS-induced neurotoxicity. Clozapine also protected neurons against 1-methyl-4-phenylpyridinium(+) (MPP(+))-induced neurotoxicity, but only in cultures containing microglia, indicating an indispensable role of microglia in clozapine-afforded neuroprotection. Further observation revealed attenuated LPS-induced microglial activation in primary neuron-glia cultures and in HAPI microglial cell line with clozapine pretreatment. Clozapine ameliorated the production of microglia-derived superoxide and intracellular reactive oxygen species (ROS), as well as the production of nitric oxide and TNF-α following LPS. In addition, the protective effect of clozapine was not observed in neuron-glia cultures from mice lacking functional NADPH oxidase (PHOX), a key enzyme for superoxide production in immune cells. Further mechanistic studies demonstrated that clozapine pretreatment inhibited LPS-induced translocation of cytosolic subunit p47(phox) to the membrane in microglia, which was most likely through inhibiting the phosphoinositide 3-kinase (PI3K) pathway. Taken together, this study demonstrates that clozapine exerts neuroprotective effect via the attenuation of microglia activation through inhibition of PHOX-generated ROS production and suggests potential use of antipsychotic drugs for neuroprotection.
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What OpenQuestion holds
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.