Silver Nanoparticle Exposure Attenuates the Viability of Rat Cerebellum Granule Cells through Apoptosis Coupled to Oxidative Stress

Abstract

The impact of silver nanoparticles (AgNPs) on the central nervous system is a topic with mounting interest and concern and the facts remain elusive. In the current study, the neurotoxicity of commercial AgNPs to rat cerebellum granule cells (CGCs) and the corresponding molecular mechanism are closely investigated. It is demonstrated that AgNPs induce significant cellular toxicity to CGCs in a dose-dependent manner without damaging the cell membrane. Flow cytometry analysis with the Annexin V/propidium iodide (PI) staining indicates that the apoptotic proportion of CGCs upon treatment with AgNPs is greatly increased compared to the negative control. Moreover, the activity of caspase-3 is largely elevated in AgNP-treated cells compared to the negative control. AgNPs are demonstrated to induce oxidative stress, reflected by the massive generation of reactive oxygen species (ROS), the depletion of antioxidant glutathione (GSH), and the increase of intracellular calcium. Histological examination suggests that AgNPs provoke destruction of the cerebellum granular layer in rats with concomitant activation of caspase-3, in parallel to the neurotoxicity of AgNPs observed in vitro. Taken together, it is demonstrated for the first time that AgNPs substantially impair the survival of primary neuronal cells through apoptosis coupled to oxidative stress, depending on the caspase activation-mediated signaling.

Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions

“…In a study on juvenile Japanese medaka (Oryzias latipes), Chae et al (2009) found that AgNPs showed higher toxicity than ionic silver after 24-and 96-h exposures. Similar result was also observed in primary granule cells in vitro (Yin et al, 2013). Moreover, some other metal nanoparticles like gold nanoparticles may not release metal ions, but caused deleterious biological effects through the induction of oxidative stress (Siddiqi et al, 2012), which hinted the particle-specific effects.…”

“…Using primary cultures of rat cerebellar granule cells (CGCs), the researchers observed that AgNPs incubation caused excitotoxicity in cultured neurons via activation of N-methyl-D-aspartate (NMDA) receptor, followed by calcium imbalance, mitochondrial dysfunction and reactive oxygen species (ROS) production (Ziemiń ska et al, 2014). Significant cellular toxicity in CGCs induced by AgNPs was mediated through programmed cell death coupled to oxidative stress (Yin et al, 2013). These proofs obtained from in vivo and in vitro tests provide the clues on how AgNPs directly interact with neurons and cause the deleterious effects.…”

Silver nanoparticle exposure induces rat motor dysfunction through decrease in expression of calcium channel protein in cerebellum

“…The primary cultured cerebellum granule cells (CGCs) were prepared according to the protocol reported previously (Yin et al, 2013). Briefly, the cerebellum granule cells dissociated from 7-dayold SD rat pups were plated in 6-well plates (1 Â10 6 cells/mL) precoated with poly-L-lysine (0.01%, Sigma-Aldrich, USA).…”

“…Mounting evidences have given some important clues to pathogenic mechanisms in cerebellum ataxia, such as disruption of voltage-gated potassium and calcium channels (Jen et al, 2007;Mori et al, 1991). Our previous study found that AgNPs exposure could attenuate the viability of rat cerebellum granule cells (CGCs) through apoptosis (Yin et al, 2013). Consequently, uncovering in vivo neurological deficits induced by AgNPs and understanding the underlying mechanism are of much significance for finding out the solution to their potential harmful effects.…”

Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia

“…As published before, nanoparticle exposure attenuates granule cell viability in vitro and in vivo, showing the vulnerability of the population. [54][55][56] Based on the result that VSOP-R2 treatment altered DG viability during long-term incubation, we hypothesize that VSOP-R2 caused oxidative stress and induced apoptosis ( Figure 2X). Because of the outcome of the aforementioned neuron-glia co-culture experiment, we assume protective effects by microglia in OHSC.…”