MITOCHONDRIAL EPIGENETIC ALTERATIONS IN HUMAN ASTROCYTES EXPOSED TO FINE PARTICULATE MATTER

Aims: Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Increasing evidence suggests that environmental factors, particularly exposure to fine particulate matter (PM2.5), contribute to AD susceptibility and progression. PM2.5 has been associated with amyloid-β accumulation, tau pathology, neuroinflammation, and cognitive impairment. However, the molecular mechanisms linking air pollution to neurodegeneration remain poorly understood. This study aimed to investigate early mitochondrial epigenetic changes induced by PM2.5 exposure in human astrocytes as a potential mechanistic link between environmental stress and AD-related pathology.
Methods: Primary human astrocytes were exposed for 24 hours to increasing concentrations (0.1–50 μg/mL) of Standard Reference Material 2786 (SRM 2786), a well-characterized PM2.5-like particulate. Cell viability was assessed by MTT assay. Mitochondrial epigenetic endpoints, including mitochondrial DNA (mtDNA) copy number, methylation of the D-loop regulatory region, and methylation of the mitochondrial ribosomal gene MT-RNR1, were evaluated using bisulfite-based methods.
Results: No significant differences in cell viability were observed following acute PM exposure. Similarly, mtDNA copy number and D-loop methylation remained unchanged across treatment conditions, indicating preserved mitochondrial content. In contrast, MT-RNR1 methylation showed a dose-dependent decreasing trend, although statistical significance was not reached.
Conclusions: Our data indicate that PM2.5 exposure induces subtle mitochondrial epigenetic alterations in human astrocytes prior to detectable cytotoxic effects. These preliminary results support the role of mitochondrial epigenetics as an early cellular response to environmental stress but more extensive research is required to validate these findings and investigate the molecular mechanisms.