Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor

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Titel: Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor
Autor(en): Grossert, Alessandra
Mehrjardi, Narges Zare
Bailey, Sarah J.
Lindsay, Mark A.
Hescheler, Jürgen
Šarić, Tomo
Teusch, Nicole
ORCID des Autors: https://orcid.org/0000-0001-8344-1095
https://orcid.org/0000-0002-9030-1493
Zusammenfassung: The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine offers promising perspectives for the treatment of major depressive disorder. Although ketamine demonstrates rapid and long-lasting effects, even in treatment-resistant patients, to date, the underlying mode of action remains elusive. Thus, the aim of our study was to investigate the molecular mechanism of ketamine at clinically relevant concentrations by establishing an in vitro model based on human induced pluripotent stem cells (iPSCs)-derived neural progenitor cells (NPCs). Notably, ketamine increased the proliferation of NPCs independent of the NMDA receptor, while transcriptome analysis revealed significant upregulation of insulin-like growth factor 2 (IGF2) and p11, a member of the S100 EF-hand protein family, which are both implicated in the pathophysiology of depression, 24 h after ketamine treatment. Ketamine (1 µM) was able to increase cyclic adenosine monophosphate (cAMP) signaling in NPCs within 15 min and cell proliferation, while ketamine-induced IGF2 expression was reduced after PKA inhibition with cAMPS-Rp. Furthermore, 24 h post-administration of ketamine (15 mg/kg) in vivo confirmed phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in the subgranular zone (SGZ) of the hippocampus in C57BL/6 mice. In conclusion, ketamine promotes the proliferation of NPCs presumably by involving cAMP-IGF2 signaling.
Bibliografische Angaben: Cells 2019, 8(10), 1139
URL: https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-202004202858
Schlagworte: human iPSC-derived NPCs; depression; neurogenesis; ketamine; IGF2; cAMP; p11
Erscheinungsdatum: 24-Sep-2019
Lizenzbezeichnung: Attribution 4.0 International
URL der Lizenz: http://creativecommons.org/licenses/by/4.0/
Publikationstyp: Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article]
Enthalten in den Sammlungen:FB08 - Hochschulschriften
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