Characterization of Perineuronal Nets (PNNs) in the Paraventricular Nucleus of the Hypothalamus (PVN) and their alteration in neurogenic hypertension

Perineuronal nets (PNNs) are key regulators of neuronal excitability, yet whether they are altered during neurogenic hypertension is unknown. Here, we mapped the developmental trajectory of PNNs in the paraventricular nucleus of the hypothalamus (PVN), a crucial nucleus involved in blood pressure regulation, and examined their modulation in neurogenic hypertension. We show that PNNs in PVN follow a developmental pattern, enwrapping 25% of neuronal nitric oxide synthase (nNOS)-expressing neurons, with sex differences observed only in oxytocin (OXT)-enwrapped populations. In the DOCA-salt mouse model of neurogenic hypertension, males, but not females, exhibit an increased number and area of PNNs in the PVN. Given that PNNs modulate neuronal activity, our findings may implicate recruitment of previously “silent” neurons as potential contributors of PVN hyperactivity in hypertension. These results demonstrate that PNN remodeling is associated with neurogenic hypertension.