PM2.5 Exposure Disrupts Sympathetic Neurotransmission by Impairing Voltage-Gated Ca2+ Channels and Remodeling Satellite Glia in the Superior Cervical Ganglion

Airborne fine particulate matter (PM2.5) exposure is associated with central neuroinflammation and autonomic dysfunction, but its effects on peripheral sympathetic ganglia remain poorly defined. Here, we examined the effects of central PM2.5 administration and direct PM2.5 exposure on the superior cervical ganglion (SCG), a primary sympathetic relay governing cephalic noradrenergic outflow. Intracerebroventricular (ICV) administration of PM2.5 increased hypothalamic TNF-α and IL-6 levels and reduced presynaptic synaptophysin expression, while SCG tyrosine hydroxylase expression remained unchanged. In a complementary ex vivo model, direct PM2.5 exposure reduced norepinephrine (NE) accumulation in the culture medium of isolated SCGs without significantly altering tissue NE content. Mechanistically, live-cell Ca2+ imaging revealed attenuated depolarization-evoked Ca2+ responses in SCG neurons following either 24-h direct exposure or in vivo ICV administration. Whole-cell patch-clamp recordings further demonstrated reduced voltage-gated Ca2+ channel (VGCC) current density in neurons isolated from ICV PM2.5-treated rats. This functional reduction was not accompanied by significant changes in the SCG mRNA levels of the examined pore-forming Cavα1 subunits. In parallel, ICV PM2.5 administration increased GFAP and Kir4.1 protein levels and enhanced perineuronal GFAP immunoreactivity, consistent with satellite glial cell reactivity. Together, these findings identify impaired neuronal Ca2+ signaling and accompanying glial alterations in the SCG following PM2.5 exposure. The reductions in extracellular NE accumulation and VGCC function across complementary exposure models support a potential contribution of impaired Ca2+-dependent secretion to PM2.5-associated sympathetic dysfunction.