Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor
Cells September 24, 2019 Alessandra Grossert, N. Mehrjardi, S. Bailey et al.
Ketamine, an NMDA receptor antagonist, shows rapid and lasting antidepressant effects even in treatment-resistant depression, but its mechanism is unclear. Using human stem cell-derived neural progenitor cells (NPCs), ketamine increased cell proliferation independently of the NMDA receptor. Transcriptome analysis revealed upregulation of IGF2 and p11, proteins linked to depression, 24 hours after treatment. Ketamine (1 µM) boosted cAMP signaling within 15 minutes and proliferation; blocking PKA reduced IGF2 expression. In mice, ketamine (15 mg/kg) confirmed ERK1/2 phosphorylation in the hippocampus. Ketamine likely promotes NPC proliferation through cAMP-IGF2 signaling.