Motor coordination dysfunction induced by gold nanorods core/silver shell nanostructures in mice: disruption in mitochondrial transport and neurotransmitter release

Abstract

The risk of exposure to silver nanoparticles (AgNPs) is becoming increasingly widespread and causes great concern. Since AgNPs induce blood–brain barrier destruction and accumulate in the brain, it is of great significance to inquire into their biological effects in the central nervous system (CNS). This study selected gold core/silver shell nanostructures (for simplicity termed as silver nanorods, AgNRs) as a model for AgNPs and investigated the neurotoxicity and mechanism in mice by single dose of intracerebroventricular (i.c.v.) administration. Behavioral changes of the mice were weekly monitored by multiple behavioral tests. Significant reduction in residence time on Rota-rod treadmills was observed for AgNRs treated mice at all the test time-points after the administration, clearly indicating a motor coordination dysfunction. Pathological examination revealed significant loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNpc) and TH-positive fibers in the striatum, which are two important brain regions regulating motor function. In primary mesencephalic neuron, both speed and percentage of mitochondrion moving in anterograde direction were decreased by AgNRs treatment, along with great reduction in neurotransmitter vesicle release efficacy. Taken together, i.c.v. administrated AgNRs impaired the nigro-striatal pathway and disrupted the mitochondrial axonal transport and neurotransmitter release may underlie the motor coordination dysfunction.