Neuron–Glia Signaling and Synaptic Remodeling in the Prehypertensive Sympathetic Ganglion

Hypertension is associated with sympathetic nervous system hyperactivity, yet the local ganglionic mechanisms contributing to this dysfunction remain poorly understood. Satellite glial cells (SGCs) closely interact with sympathetic neurons in peripheral ganglia and regulate synaptic development and transmission, suggesting a potential role in circuit remodeling. This study investigated whether neuron-glia signaling is altered in a neurogenic rat model of hypertension, as well as evaluated the role of TNF-α signaling in synaptic organization in both healthy and disease-relevant contexts. Neuron-glia cocultures and glia-only cultures were prepared from the superior cervical ganglia of Spontaneously Hypertensive Rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Quantitative PCR revealed reduced nerve growth factor (NGF) expression in SHR cocultures and increased expression in SHR glia-only cultures, suggesting altered neuron-dependent regulation of NGF. TNF-α expression was similar between strains in cocultures but elevated in SHR glia-only conditions, indicating potential differences in neuronal regulation of glial cytokine signaling. Pharmacological blockade of TNFR1 using R7050 was associated with strain-dependent changes in synaptic densities, although these effects were not consistently statistically significant. Chemogenetic activation of sympathetic neurons did not significantly alter presynaptic or postsynaptic puncta density, but treatment conditions were associated with significant decreases in colocalized puncta density.