Polystyrene microplastics (PS-MPs) are ubiquitous environmental contaminants repeatedly shown to impair cognitive function in mouse models. Existing litera ture converges on oxidative stress, blood-brain barrier disruption, and neuroin f lammation as central mechanisms, yet the precise molecular pathways linking these phenomena to hippocampal dysfunction remain incompletely understood. This review synthesizes current evidence to evaluate the hypothesis that PS-MP exposure triggers a metabolic shift toward aerobic glycolysis, enhancing lactate production. This lactate, in turn, may mediate neuroinflammation and impair synaptic plasticity through epigenetic reprogramming via histone lactylation (e.g., H3K18la). We construct a mechanistic model based on this hypothesis, inte grating findings on microglial activation, astrocyte-neuron metabolic coupling, and innate immune signaling. While the glycolysis-lactate-histone lactylation axis presents a biologically plausible mechanism for PS-MP neurotoxicity, we iden tify critical evidence gaps, primarily the lack of direct measurements of lactate, glycolytic flux, and histone lactylation in the brain following PS-MP exposure. Finally, we propose key regulatory proteins—including LDHA, MCTs, p300, and HIF-1α—as high-priority targets for future research to validate this emerging metabolic-epigenetic pathway.