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

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-concentration treatments increased intracellular adenosine triphosphate (ATP) levels in microglia and enhanced microglia-mediated activation of neuronal NFE2L2. In contrast, high NP concentrations impaired microglial metabolism, reduced ATP availability, and decreased microglial-neuronal communication. These findings indicate that NPs alter microglial energetic status and modulate neuroprotective signaling, potentially contributing to impaired neuron-microglia interactions and increased susceptibility to neurotoxicity.