Nitrogen Doping Reduces the Neurotoxic Effects of Graphene Quantum Dots by Suppressing Proinflammatory and Oxidative Stress Pathways

Abstract

Graphene quantum dots (GQDs) and their nitrogen-doped counterparts (N-GQDs) have recently been explored in the management of neurological disorders. However, their biocompatibility remains questionable, particularly subsequent to direct brain exposure. In this study, we investigated the neurotoxicity of GQDs and N-GQDs in neuroblastoma cells and healthy mice. The change in the viability of SH-SY5Y cells was examined at different doses of quantum dots. Later, these were injected into the animals via the intracerebroventricular route, and neurobehavioral tests and biochemical assays were performed. Apart from histological examinations, immunohistochemical staining of tissue sections was carried out to assess impairment in brain function and delineate the underlying mechanism. We noticed significantly higher cell death and neurobehavioral impairment in the presence of GQDs. Signs of oxidative stress and neuroinflammation were evident from the upregulation of oxidative stress markers (GSH and MDA), inflammatory mediators (TNF-α and IL-1β), and glial activation. Neurotoxicity of GQDs could further be confirmed from the data of Nissl’s, hematoxylin and eosin, and Luxol fast blue staining experiments. On the contrary, neuronal morphology of the hippocampal region and myelinated structures looked well-preserved in N-GQD-treated animals. Altogether, we conclude that nitrogen-doped quantum dots could protect the animals against depletive neurobehavioral changes.