Valproic acid (VPA) is one of the main anticonvulsive drugs used worldwide for the treatment of epilepsy. Its use and clinical benefits are acknowledged; however, apparent effects of VPA on mitochondria vary among cell types and methods of analysis. Automated fluorescence microscopy offers stable, reproducible, and expandable assays useful for identifying mitochondrial responses to drugs. Here we have used human neural progenitor cells (NPCs) derived from embryonic stem cells to evaluate neural mitochondrial responses to VPA. We have analyzed the effects of different concentrations of VPA (from 0.01 to 1 mM) on mitochondria morphology and inferred membrane potential, as well as shape and content distribution. Our results show that following exposure to VPA the morphological and functional alterations observed in NPC mitochondria were consistent with prior reports for such effects. Changes detected include mitochondria shape from filamentous to globular and increases in mitochondrial membrane potential. This in vitro preparation provides new clues and expanded opportunities for studying the mode of action and toxicity of clinically approved compounds in human brain cells where mitochondrial morphology, in particular, may offer a powerful indicator amenable to high-throughput methods.
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