Influence of Air Pollution Exposure on the microRNA Content of Neuronal Extracellular Vesicles in Subjects Affected by Major Depressive Disorder

Major depressive disorder (MDD) has been recently linked
to air
pollution exposure; nevertheless, the biological mechanisms underlying
this association remain underinvestigated. Air pollution might modulate
the microRNA (miRNA) content of neuron-derived extracellular vesicles
(NdEVs), potentially mirroring brain epigenetic alterations. In the
present study, we investigated the relationship between air pollution,
NdEV miRNAs, and MDD severity in a population of 200 patients with
depression. After signing informed consent, participants compiled
questionnaires about demographics, lifestyle and clinical history,
and donated a blood sample. MDD severity was assessed by five scales.
Particulate matter ≤2.5 μm (PM2.5) and nitrogen
dioxide (NO2) exposure was assigned based on participants’
residential address. Plasma NdEVs were obtained by L1CAM immunocapture.
NdEV miRNAs were queried by RT-qPCR (microarray) following a two-stage
approach. Associations between air pollutants, NdEV miRNAs, and MDD
severity were assessed by multivariable regression models. The regulatory
function of NdEV miRNAs was investigated by gene target and pathway
analysis. As a result, exposure to NO2 was associated with
decreased levels of miR-191 and miR-24, while PM2.5 was
negatively associated with miR-191, miR-223, miR-24, miR-320, miR-451,
miR-572, and miR-638. Decreased miR-126, miR-19b, miR-320, miR-451,
miR-572, and miR-638 were associated with higher MDD severity scores.
Target genes at the interface between air pollution exposure and MDD
severity were mainly involved in inflammation and cell cycle regulation.
These findings suggest that air pollutants might modulate MDD severity
by triggering NdEV miRNA alterations. Longitudinal studies are needed
to evaluate whether NdEV miRNAs might serve as novel biomarkers for
MDD prognosis.