Titanium Dioxide Nanoparticles Induce Cognitive Dysfunction of Rats with Endogenous Protective Mechanism of Increased miR-21-5p

Abstract BackgroundTitanium dioxide nanoparticles (TiO 2 NPs) cause nerve cell damage and central nervous system dysfunction has been well known. However, most of the cognitive deficits occurs before the observable damage to nerve cells and the regulatory mechanism is largely unknown. Mitochondria and energy metabolism are the targets of many neurotoxic substances. ResultsHere, we showed that TiO 2 NPs exposure reduced the mitochondrial membrane potential (ΔΨm) and ATP content, which is the important cause of cognitive deficits, and upregulated microRNA-21-5p (miR-21-5p) levels in rat neuron cells. Upregulated miR-21-5p promoted phosphorylation of c-Jun, consequently promoting transcription of VDAC1 (encoding voltage-dependent anion channel 1), which in turn preserved the ΔΨm and ATP content of neuron cells. ConclusionsMechanistically, upregulated VDAC1 was attributed to TiO 2 NPs-induced phosphorylation of c-Jun (Ser73), which is predicted to be a transcription factor of VDAC1 , while upregulation of the ΔΨm and ATP content was caused by the increased oxygen consumption rate induced by VDAC1. The results of our present study revealed an endogenous self-protection mechanism in the process of TiO 2 NPs-induced cognitive deficits.