Deformation of mitochondrial cristae in human neural progenitor cells exposed to valproic acid

Abstract

Neural development represents a dynamic process where mitochondrial integrity is decisive for neuronal activity. Structural changes in these organelles may be related to neurological disorders. Valproic acid (VPA) is an anticonvulsive drug commonly used for epilepsy treatment and its use is associated to increased risk of neuropsychiatric disorders. Recently we showed changes in shape and membrane potential in mitochondria from human neural progenitor cells (NPCs) exposed to VPA (da Costa et al. 2015). Here, we applied transmission electron microscopy and electron tomography to evaluate mitochondrial damage caused by VPA in NPCs. Results showed mitochondrial cristae disorganization in a dose dependent manner. Disturbance in mitochondrial ultrastructure may influence metabolism, leading to synaptic plasticity and neurogenesis impairment. These data contribute to understanding VPA exposure potential effects on brain development.