Do nanoplastics reshape microglial support of neuronal resilience? A study of microglial bioenergetics and microglia to neuron communication in vitro

Abstract

Nanoplastics (NPs) are emerging environmental contaminants able to cross biological barriers, disrupt cellular and organelle homeostasis, and alter the brain microenvironment. This study investigated whether NPs affect microglia-neuron communication, a key mechanism underlying neuronal resilience, via the nuclear factor erythroid 2-like 2 (NFE2L2) pathway. Using an in vitro model, we evaluated the effects of polystyrene nanoplastics on microglial metabolic fitness and microglia-mediated neuronal stress responses. Increasing NP concentrations induced a dose-dependent biphasic effect. Low to intermediate concentrations increased intracellular adenosine triphosphate (ATP) levels in microglia and enhanced microglia-mediated activation of neuronal NFE2L2. In contrast, high NP concentration impaired microglial metabolism, reduced ATP availability, and decreased microglia-neuron communication. These findings indicate that NPs alter microglial energetic status and modulate neuroprotective signalling, potentially contributing to impaired neuron-microglia interactions and increased susceptibility to neurotoxicity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/732827v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@d33f79org.highwire.dtl.DTLVardef@ec4542org.highwire.dtl.DTLVardef@1b71ca3org.highwire.dtl.DTLVardef@b92ad4_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LINanoplastics alter microglial metabolic fitness in vitro. C_LIO_LINanoplastics biphasically modulate microglial support of neurons. C_LIO_LIHigh nanoplastic concentration reduces microglial support to neurons. C_LIO_LIMicroglial bioenergetics may link nanoplastics to neuronal vulnerability. C_LI