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dc.date.accessioned2018-09-05T14:39:13Z
dc.date.available2018-09-05T14:39:13Z
dc.date.created2017-06-08T12:52:37Z
dc.date.issued2017
dc.identifier.citationMansouri, Shiva Agartz, Ingrid Ögren, Sven-Ove Patrone, Cesare Lundberg, Mathias . PACAP protects adult neural stem cells from the neurotoxic effect of ketamine associated with decreased apoptosis, ER stress and mTOR pathway activation. PLoS ONE. 2017, 12(1), 1-16
dc.identifier.urihttp://hdl.handle.net/10852/64138
dc.description.abstractKetamine administration is a well-established approach to mimic experimentally some aspects of schizophrenia. Adult neurogenesis dysregulation is associated with psychiatric disorders, including schizophrenia. The potential role of neurogenesis in the ketamine-induced phenotype is largely unknown. Recent results from human genetic studies have shown the pituitary adenylate cyclase-activating polypeptide (PACAP) gene is a risk factor for schizophrenia. Its potential role on the regulation of neurogenesis in experimental model of schizophrenia remains to be investigated. We aimed to determine whether ketamine affects the viability of adult neural stem cells (NSC). We also investigated whether the detrimental effect mediated by ketamine could be counteracted by PACAP. NSCs were isolated from the subventricular zone of the mouse and exposed to ketamine with/without PACAP. After 24 hours, cell viability, potential involvement of apoptosis, endoplasmic reticulum (ER) stress, mTOR and AMPA pathway activation were assessed by quantitative RT-PCR and Western blot analysis. We show that ketamine impairs NSC viability in correlation with increased apoptosis, ER stress and mTOR activation. The results also suggest that the effect of ketamine occurs via AMPA receptor activation. Finally, we show that PACAP counteracted the decreased NSC viability induced by ketamine via the specific activation of the PAC-1 receptor subtype. Our study shows that the NSC viability may be negatively affected by ketamine with putative importance for the development of a schizophrenia phenotype in the ketamine induced animal model of schizophrenia. The neuroprotective effect via PAC-1 activation suggests a potentially novel pharmacological target for the treatment of schizophrenia, via neurogenesis normalization.en_US
dc.languageEN
dc.language.isoenen_US
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titlePACAP protects adult neural stem cells from the neurotoxic effect of ketamine associated with decreased apoptosis, ER stress and mTOR pathway activationen_US
dc.typeJournal articleen_US
dc.creator.authorMansouri, Shiva
dc.creator.authorAgartz, Ingrid
dc.creator.authorÖgren, Sven-Ove
dc.creator.authorPatrone, Cesare
dc.creator.authorLundberg, Mathias
cristin.unitcode185,53,10,11
cristin.unitnameSenter for psykoseforskning
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1474733
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=12&rft.spage=1&rft.date=2017
dc.identifier.jtitlePLoS ONE
dc.identifier.volume12
dc.identifier.issue1
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0170496
dc.identifier.urnURN:NBN:no-66666
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1932-6203
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/64138/2/mansouri.pdf
dc.type.versionPublishedVersion
cristin.articleide0170496


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