The glycolytic shift was involved in CdTe/ZnS quantum dots inducing microglial activation mediated through the mTOR signaling pathway

Abstract

The excellent optical property and relatively low toxicity of CdTe/ZnS core/shell quantum dots (QDs) make them an advanced fluorescent probe in the application of biomedicines, particularly in neuroscience. Thus, it is important to evaluate the biosafety of CdTe/ZnS QDs on the central nervous system (CNS). Our previous studies have suggested that the high possibility of CdTe/ZnS QDs being transported into the brain across the blood‐brain barrier resulted in microglial activation and a shift of glycometabolism, but their underlying mechanism remains unclear. In this study, when mice were injected intravenously with CdTe/ZnS QDs through tail veins, the microglial activation, polarized into both M1 phenotype and M2 phenotype, and the neuronal impairment were observed in the hippocampus. Meanwhile, the increased pro‐ and anti‐inflammatory cytokines released from BV2 microglial cells treated with CdTe/ZnS QDs also indicated that QD exposure was capable of inducing microglial activation in vitro. We further demonstrated that the glycolytic shift from oxidative phosphorylation switching into aerobic glycolysis was required in the microglial activation into M1 phenotype induced by CdTe/ZnS QD treatment, which was mediated through the mTOR signaling pathway. The findings, taken together, provide a mechanistic insight regarding the CdTe/ZnS QDs inducing microglial activation and the role of the glycolytic shift in it.

<p>The NLRP3-Mediated Neuroinflammatory Responses to CdTe Quantum Dots and the Protection of ZnS Shell</p>

“…17,18 The physicochemical properties of CdTe QDs and CdTe@ZnS QDs were evaluated as the method described in a previous study. 12 All characteristic data of QDs are presented in Table S1 and Figure S1.…”

“…Although our research group has shown the roles of sizes and surface coatings influencing the neuroinflammatory reactions to CdTe QDs in neuronal cells, 12,13 the neuroinflammation-promoting effects of CdTe QDs in in vivo biological models are still not clear. In this study, two animal models, ie, Caenorhabditis elegans and Institute of Cancer Research (ICR) mice, were used.…”

Glycometabolism Reprogramming of Glial Cells in Central Nervous System: Novel Target for Neuropathic Pain

“…Upon infection, injury or stress, microglia migrate to the site of inflammation, assume an amoeboid shape and secrete cytokines, chemokines and ROS ( 88 ). Metabolic changes in neurons and glial cells upon injury or stress (e.g., lactate, succinate and citric acid) are important in the formation of synaptic plasticity in pain sensitization and neuropathic pain, as well as a variety of other central nervous system diseases ( 89 ).…”

Research progress in the synthesis and biological application of quantum dots

“…86 Wu and colleagues found that when CdTe/ZnS QDs were injected into the tail vein of mice to observe the activation of hippocampal microglia, the microglia were transformed into M1 and M2 phenotypes, resulting in neuron damage. 87 Caenorhabditis elegans has emerged as a biological model for the study of neurotoxicity in vivo due to its strong reproductive capacity, transparent body, simple neural structure and low cost. CdTe quantum dots have been reported to cause damage to the nervous system of C. elegans .…”