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

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

bioRxiv (Cold Spring Harbor Laboratory) 2026
Electra Brunialti, Clara Meda, Alessandro Villa, Marco Parolini, Paolo Ciana, Lavinia Casati

Summary

Scientists exposed brain cells in a lab dish to tiny plastic particles (nanoplastics) to see how they affect microglia—immune cells that support and protect neurons. They found that low amounts of plastic actually boosted microglia's energy levels and their ability to help neurons handle stress, but high amounts overwhelmed the cells' energy production and weakened this protective support. This suggests that as nanoplastic exposure builds up, it could make brain cells more vulnerable to damage—though this was shown in cells in a dish, not in living animals or people, so more research is needed to know what this means for human brain health.

Polymers
Body Systems
Study Type 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. Abstract Figure Highlights Nanoplastics alter microglial metabolic fitness in vitro . Nanoplastics biphasically modulate microglial support of neurons. High nanoplastic concentration reduces microglial support to neurons. Microglial bioenergetics may link nanoplastics to neuronal vulnerability.

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