Central neuroplasticity and decreased heart rate variability after particulate matter exposure in mice

Abstract

Background: Epidemiologic studies show that exposure to fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] increases the total daily cardiovascular mortality. Impaired cardiac autonomic function, which manifests as reduced heart rate variability (HRV), may be one of the underlying causes. However, the cellular mechanism(s) by which PM2.5 exposure induces decreased HRV is not known. Objectives: We tested the hypothesis that exposure to PM2.5 impairs HRV by decreasing the excitability of the cardiac vagal neurons in the nucleus ambiguus. We also detemined the effect of iron on PM-exposure-induced decrease in HRV. Methods: We measured 24-hr HRV in time domains from electrocardiogram telemetry recordings obtained in conscious, freely moving mice after 3 days of exposure to PM2.5 in the form of soot only or iron-soot. In parallel studies, we determined the intrinsic properties of identified cardiac vagal neurons, retrogradely labeled with a fluorescent dye applied to the sinoatrial node. Results: Soot-only exposure decreased short-term HRV (root mean square of successive difference). With the addition of iron, all HRV parameters were significantly reduced. In nonexposed mice, vagal blockade significantly reduced all HRV parameters, suggesting that HRV is, in part, under vagal regulation in mice. Iron-soot exposure had no significant effect on resting membrane potential but decreased spiking responses of the identified cardiac vagal neurons to depolarizations (p < 0.05). The decreased spiking response was accompanied with a higher minimal depolarizing current required to evoke spikes and a lower peak discharge frequency. Conclusions: The data suggest that PM-induced neuroplasticity of cardiac vagal neurons may be one mechanism contributing to the cardiovascular consequences associated with PM2.5 exposure seen in humans.