Characterization of Perineuronal Nets in the Paraventricular Nucleus of the Hypothalamus 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 (BP) regulation, and examined their modulation in neurogenic hypertension. We show that PNNs in the PVN follow a developmental pattern similar to other brain regions. The most prevalent neuron subtype enwrapped by PNNs was neuronal nitric oxide synthase (nNOS)-expressing neurons in both sexes, and sex differences were observed only in oxytocin (OXT)-enwrapped neurons. In the DOCA-salt mouse model of neurogenic hypertension, males, but not females, exhibit an increased number and area of PNNs in the PVN with increased excitatory/inhibitory (E/I) ratio. 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 in male mice.