Prenatal exposure to titanium dioxide nanoparticles induces persistent neurobehavioral impairments in maternal mice that is associated with microbiota-gut-brain axis

Abstract

Gestational exposure to titanium dioxide nanoparticles (TiO₂NPs) has been widely reported to have deleterious effects on the brain functions of offspring. However, little attention has been paid to the neurotoxic effects of TiO₂NPs on maternal body after parturition. The pregnant mice were orally administrated with TiO₂NPs at 150 mg/kg from gestational day 8-21. The potential effects of TiO₂NPs on the neurobehaviors were evaluated at postnatal day 60. The gut microbiota, morphological alterations of intestine and brain, and other indicators that involved in gut-brain axis were all assessed to investigate the underlying mechanisms. The results demonstrated that exposure to TiO₂NPs during pregnancy caused the persistent neurobehavioral impairments of maternal mice after delivery for 60 days, mainly including behavioural changes, pathological changes in hippocampus, cortex and intestine. Our data also showed that persistent dysfunction and tissue injuries were probably associated with the disruption of gut-brain axis, manifested by the shift in the composition of gut microbial community, alteration of Sstr1, inhibition of enteric neurons and reduction of diamine oxidase contents in maternal mice. These findings provide a novel insight that regulation of gut microecology may be an alternative strategy for the protection against the neurotoxicity of TiO₂NPs in pregnant women.

Keywords: Dysbiosis; Gut microbiota; Neurobehavioral impairments; Pregnancy exposure; Titanium dioxide nanoparticles.