Urban air pollution reduces H3K9me2/me3 in hippocampal and olfactory neurons, correlating with memory and social deficits

Abstract

Air pollution, particularly fine particulate matter and ultrafine particles, has been strongly associated with cognitive impairments and neurodegenerative diseases. These effects are mediated by mechanisms such as neuroinflammation, oxidative stress, and alterations in the transcriptional machinery. Although evidence indicates that particulate matter influences brain epigenetics, its effects on brain function and behavior remain poorly understood. In this study, we employed a ‘real-world’ exposure model to assess the impact of urban air pollution on behavior, epigenetic modifications and neuroinflammation in mice. We found that mice exposed to air pollution exhibited behavioral impairments, including deficits in spatial and social memory, and signs of anxiety and despair. These changes were accompanied by a decrease in the repressive histone post-translational modifications H3K9me3 and H3K9me2 in the hippocampus and olfactory bulb, regions critical for memory and sensory processing. Furthermore, these regions also showed increased astrogliosis, indicative of neuroinflammation. Our findings highlight the role of particulate matter in driving behavioral deficits through epigenetic dysregulation and neuroinflammation in key brain regions. This study emphasizes the importance of addressing air quality to protect cognitive health and mitigate neurodegenerative processes, which may contribute to the initiation of Alzheimer's disease.