ArticleBioscience reports2020
Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy.
Article in Bioscience reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation.Molecules (Basel, Switzerland) · 2026Article
- Protective effects of curcumin/magnesium oxide nanoparticles on ketamine-induced neurotoxicity in the mouse hippocampus.Research in pharmaceutical sciences · 2025Article
- Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug.Brain sciences · 2024Review
- Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- Neurotoxic/Neuroprotective Effects of Clozapine and the Positive Allosteric Modulator of mGluR2 JNJ-46356479 in Human Neuroblastoma Cell Cultures.International journal of molecular sciences · 2023Article
- Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia.Antioxidants (Basel, Switzerland) · 2022Review
- Clozapine induces astrocyte-dependent FDG-PET hypometabolism.European journal of nuclear medicine and molecular imaging · 2022Article
- Clozapine Increases Nestin Concentration in the Adult Male Rat Hippocampus: A Preliminary Study.International journal of molecular sciences · 2022Article
- Review
- Autophagy Inhibition by ATG3 Knockdown Remits Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury and Inflammation in Brain Microvascular Endothelial Cells.Neurochemical research · 2021Article
- Chlorpromazine affects the numbers of Sox-2, Musashi1 and DCX-expressing cells in the rat brain subventricular zone.Pharmacological reports : PR · 2021Article
- Pharmacological Potentiality of Bioactive Flavonoid against Ketamine Induced Cell Death of PC 12 Cell Lines: An In Vitro Study.Antioxidants (Basel, Switzerland) · 2021Article
- Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia.Translational psychiatry · 2021Review
- The protective effect of olanzapine on ketamine induced cognitive deficit and increased NR1 expression in rat model of schizophrenia.International journal of physiology, pathophysiology and pharmacology · 2021Article
- The Ketamine Antidepressant Story: New Insights.Molecules (Basel, Switzerland) · 2020Review
- The Unfolded Protein Response and Autophagy as Drug Targets in Neuropsychiatric Disorders.Frontiers in cellular neuroscience · 2020Review
- A Review of Nonanesthetic Uses of Ketamine.Anesthesiology research and practice · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adult neurogenesis, the production of newborn neurons from neural stem cells (NSCs) has been suggested to be decreased in patients with schizophrenia. A similar finding was observed in an animal model of schizophrenia, as indicated by decreased bromodeoxyuridine (BrdU) labelling cells in response to a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist. The antipsychotic drug clozapine was shown to counteract the observed decrease in BrdU-labelled cells in hippocampal dentate gyrus (DG). However, phenotypic determination by immunohistochemistry analysis could not reveal whether BrdU-positive cells were indeed NSCs. Using a previously established cell model for analysing NSC protection in vitro, we investigated a protective effect of clozapine on NSCs. Primary NSCs were isolated from the mouse subventricular zone (SVZ), we show that clozapine had a NSC protective activity alone, as evident by employing an ATP cell viability assay. In contrast, haloperidol did not show any NSC protective properties. Subsequently, cells were exposed to the non-competitive NMDA-receptor antagonist ketamine. Clozapine, but not haloperidol, had a NSC protective/anti-apoptotic activity against ketamine-induced cytotoxicity. The observed NSC protective activity of clozapine was associated with increased expression of the anti-apoptotic marker Bcl-2, decreased expression of the pro-apoptotic cleaved form of caspase-3 and associated with decreased expression of the autophagosome marker 1A/1B-light chain 3 (LC3-II). Collectively, our findings suggest that clozapine may have a protective/anti-apoptotic effect on NSCs, supporting previous in vivo observations, indicating a neurogenesis-promoting activity for clozapine. If the data are further confirmed in vivo, the results may encourage an expanded use of clozapine to restore impaired neurogenesis in schizophrenia.
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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.