Universität zu Köln

Grossert, Alessandra, Mehrjardi, Narges Zare, Bailey, Sarah J., Lindsay, Mark A., Hescheler, Juergen, Saric, Tomo and Teusch, Nicole ORCID: 0000-0002-9030-1493 (2019). Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor. Cells, 8 (10). BASEL: MDPI. ISSN 2073-4409

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Abstract

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 mu M) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grossert, Alessandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehrjardi, Narges Zare UNSPECIFIED UNSPECIFIED UNSPECIFIED Bailey, Sarah J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindsay, Mark A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED UNSPECIFIED UNSPECIFIED Teusch, Nicole UNSPECIFIED orcid.org/0000-0002-9030-1493 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-131922
DOI:	10.3390/cells8101139
Journal or Publication Title:	Cells
Volume:	8
Number:	10
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIPPOCAMPAL NEUROGENESIS; NEUROTROPHIC FACTOR; BRAIN; STRINGTIE; HISAT; CAMP Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13192