The potential health impacts of nanoplastic exposure have attracted significant scientific interest, with emerging evidence linking their presence to various human diseases. Alarmingly, polystyrene nanoplastics (PS-NPs) have been detected in brain tissues, showing their capability to penetrate the blood-brain barrier (BBB). However, most previous animal studies used high-dose acute exposures, which may not properly reflect the common long-term, low-dose exposure scenarios in real-world. Thus, we conducted a 17-month exposure study in mice using PS-NPs with significantly lower dosage and assessed their behavior and brain damage. Our results demonstrated that prolonged exposure induced oxidative stress in the brain with significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as activated immune responses, including microglial activation (Iba1+) and increased release of inflammatory cytokines, indicating a chronic inflammatory state in the brain. In behavioral experiments, only the EPM showed significant differences, however, pathways linked to neurodegenerative diseases like Parkinson's were notably upregulated. This unfavorable molecular network restructuring may heighten the risk for such disorders. These findings provide critical evidence for the adverse neural effects of long-term, low-dose PS-NPs exposure, thus laying the ground for further more detailed investigation and offering insights for future health interventions and preventive strategies.