دورية أكاديمية
Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy
| العنوان: | Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy |
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| المؤلفون: | Lundberg, Mathias, Curbo, Sophie, Bohman, Hannes, Agartz, Ingrid, Ögren, Sven-Ove, Patrone, Cesare, Mansouri, Shiva |
| المصدر: | 0144-8463. |
| بيانات النشر: | Kluwer Academic/Plenum Publishers |
| سنة النشر: | 2021 |
| المجموعة: | Universitet i Oslo: Digitale utgivelser ved UiO (DUO) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | http://urn.nb.no/URN:NBN:no-87625Test; Lundberg, Mathias Curbo, Sophie Bohman, Hannes Agartz, Ingrid Ögren, Sven-Ove Patrone, Cesare Mansouri, Shiva . Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy. Bioscience Reports. 2020, 40(1); http://hdl.handle.net/10852/84932Test; 1888938; info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Bioscience Reports&rft.volume=40&rft.spage=&rft.date=2020; Bioscience Reports; 40; 11; https://doi.org/10.1042/BSR20193156Test; URN:NBN:no-87625; Fulltext https://www.duo.uio.no/bitstream/handle/10852/84932/1/Clozapine%2Bprotects%2Badult%2Bneural%2Bstem%2Bcells%2Bfrom%2Bketamine-induced%2Bcell%2Bdeath%2Bin%2Bcorrelation%2Bwith%2Bdecreased%2Bapoptosis%2Band%2Bautophagy.pdfTest |
| DOI: | 10.1042/BSR20193156 |
| الإتاحة: | https://doi.org/10.1042/BSR20193156Test http://hdl.handle.net/10852/84932Test http://urn.nb.no/URN:NBN:no-87625Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.A85407D0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1042/BSR20193156 |
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