Ketamine causes mitochondrial dysfunction in human induced pluripotent stem cell-derived neurons.

ABSTRACT:

Purpose

Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated.

Methods

Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy.

Results

Twenty-four-hour exposure of i

SUBMITTER: Ito H 

PROVIDER: S-EPMC4447382 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature