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Graphene quantum dots (GQDs) have been broadly applied in biomedicine in recent years. So far, researches have reported that GQDs might contribute to the injury of the central nervous system (CNS), yet the latent toxicological mechanism is not clear. This study aims to investigate the underlying biological mechanism responsible for the neurotoxicity of nitrogen-doped GQDs (N-GQDs) and amino-functionalized GQDs (A-GQDs) by use of genome-wide transcription microarray. The findings showed that 174 and 1341 genes were altered significantly in the BV2 cells treated by 25 μg/mL N-GQDs and 100 μg/mL N-GQDs compared with the control, respectively. As for the BV2 cells exposed to 100 μg/mL A-GQDs, 1396 diversely expressed genes were detected. By comparing the 100 μg/mL N-GQDs exposed group with 100 μg/mL A-GQDs exposed group, the expression of 256 genes was extensively altered, including 58 upregulated genes and 198 downregulated genes. From Gene Ontology (GO) analysis, the altered genes were mainly enriched in functions of ion channel activation and cellular processes. Based on the KEGG pathway and signal-net analysis, the toxicity of GQDs in BV2 cells was closely related to calcium signaling pathway, cell cycle and endocytosis. And the pathways that the shared mRNAs involved all served as the crucial roles in the neurotoxicity of GQDs despite the chemical functionalization (N-GQDs or A-GQDs). In addition, the consequences from qRT-PCR, Western blot, intracellular calcium level measurements and comet assay further confirmed that calcium dyshomeostasis, DNA damage and cell cycle arrest were the key factors responsible for the GQDs-induced neurotoxicity through affecting several classical signaling pathways. In conclusion, our research will supply essential data for further studies on mechanisms of GQDs-induced neurotoxicity by use of genome-wide screening. Unlabelled Image • The altered genes were mainly involved in ion channel activity and cellular processes. • GABAergic synapse, calcium signaling pathway, tyrosine metabolism and cell cycle might be the toxic pathways of GQDs. • The severer neurotoxicity of N-GQDs than A-GQDs on BV2 cells might be from the maladjustment of Ubiquinone pathway. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) could accumulate in the central nervous system (CNS) and induce neurotoxicity for their widespread use in industry and medicine. Mitochondria are vulnerable to toxicity of AgNPs, however, their role in the neurotoxicity remains unclear. This study aimed to evaluate AgNPs-induced synaptic degeneration in mouse hippocampal neurons (at a dose of 12–120 mg/kg BW via intravenous injection), and to further investigate mechanism of mitophagy, mitochondrial biogenesis process in the neurotoxicity. The results indicated that AgNPs accumulated in mouse hippocampal neurons and induced neurological deficits of learning and memory, which involved in synaptic degeneration accompanied with mitochondrial damage. Mechanistically, AgNPs exposure increased protein expression of PTEN-induced kinase 1 (PINK1), Parkin and inhibited peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1 α) protein expression, caused disturbed mitophagy and mitochondrial biogenesis. AgNPs also induced synaptic damage by increasing the protein expression of synaptophysin and decreasing PSD95, MAP2 protein expression. AgNPs exposure even promoted protein expression of amyloid precursor protein (APP) using in amyloid- β (A β) cleavage. Furthermore, AgNPs induced hippocampal neuronal synaptic degeneration, mitophagy and mitochondrial biogenesis is dependent on particle-specific AgNPs rather than released silver ions. Our research could provide insights into the regulatory mechanisms of AgNPs-induced neurotoxicity. This study will shed the light of neurotoxicological evaluation of nanoparticles and possible early warning of biomedical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Along with the rapidly increasing applications of nitrogen-doped graphene quantum dots (N-GQDs) in the field of biomedicine, the exposure of N-GQDs undoubtedly pose a risk to the health of human beings, especially in the nervous system. In view of the lack of data from in vivo studies, this study used the nematode Caenorhabditis elegans (C. elegans), which has become a valuable animal model in nanotoxicological studies due to its multiple advantages, to undertake a bio-safety assessment of N-GQDs in the nervous system with the assistance of a deep learning model. The findings suggested that accumulated N-GQDs in the nematodes' bodies damaged their normal behavior in a dose- and time-dependent manner, and the impairments of the nervous system were obviously severe when the exposure dosages were above 100 μg/mL. When assessing the morphological changes of neurons caused by N-GQDs, a quantitative image-based analysis based on a deep neural network algorithm (YOLACT) was used because traditional image-based analysis is labor-intensive and limited to qualitative evaluation. The quantitative results indicated that N-GQDs damaged dopaminergic and glutamatergic neurons, which are involved in the neurotoxic effects of N-GQDs in the nematode C. elegans. This study not only suggests a fast and economic C. elegans model to undertake the risk assessment of nanomaterials in the nervous system, but also provides a valuable deep learning approach to quantitatively track subtle morphological changes of neurons at an unbiased level in a nanotoxicological study using C. elegans. [ABSTRACT FROM AUTHOR]