Increased BDNF Expression in the Paraventricular Nucleus of the Hypothalamus (PVN) Abolishes Hypotensive Actions of Nucleus of the Solitary Tract (NTS) Catecholaminergic Neurons
Authors: Erdos Benedek , Cruickshank Nick C , Einwag Zachary D , Schaich Chris L , Wellman Theresa L 
Published: November 2023

Brain derived neurotrophic factor (BDNF) expression in the PVN increases in response to hypertensive stimuli including stress, and we have recently shown that BDNF is a significant pro‐hypertensive mediator in the PVN. However, the downstream mechanisms mediating this effect of BDNF remain to be investigated. BDNF is an important modulator of catecholaminergic neuronal function throughout the central nervous system; therefore it could potentially influence catecholaminergic input into the PVN as well. The majority of catecholaminergic projections to the PVN originate from the NTS, and these neurons have been shown to exert hypotensive actions. Here, we tested the hypothesis that increased BDNF levels in the PVN elevate blood pressure in part by diminishing the hypotensive influence of NTS catecholaminergic neurons projecting to the PVN. Sprague‐Dawley rats received bilateral PVN injections of AAV2 viral vectors expressing either green fluorescent protein (GFP) or BDNF and bilateral NTS injections of phosphate‐buffered saline (PBS) or anti‐dopamine‐β‐hydroxylase‐conjugated saporin (DSAP, 22ng in 100nL), a neurotoxin selective to noradrenaline‐ and adrenaline‐synthesizing neurons. Blood pressure was monitored with telemetry during baseline conditions and during acute restraint stress. Our results showed that BDNF treatment significantly increased resting daytime mean arterial pressure (MAP). MAP was 115±3 mmHg in the BDNF+PBS group compared with 96±2 mmHg in the GFP+PBS group (p<0.01) 3 wks after injections. Lesioning NTS catecholaminergic neurons with DSAP also increased daytime MAP in GFP‐treated rats (GFP+DSAP: 109±3 mmHg, p<0.05 vs GFP+PBS), but failed to induce further MAP increases in the BDNF group (BDNF+DSAP: 115±4 mmHg, p>0.99 vs BDNF+PBS). Furthermore, BDNF overexpression reduced spontaneous baroreflex sensitivity in rats receiving PBS injections into the NTS, and DSAP reduced baroreflex sensitivity in GFP rats. However, DSAP failed to have an effect in the BDNF group. Heart rate was increased by BDNF overexpression, and in contrast to MAP, heart rate was elevated by DSAP both in GFP‐ and BDNF‐treated rats, although the tachycardic effect was reduced in the BDNF group. Restraint stress‐induced pressor responses were significantly elevated by DSAP in GFP rats, whereas the increase in heart rate was reduced. In contrast, DSAP had no effect on either of these parameters in the BDNF group. Finally, immunohistochemistry indicated that BDNF overexpression in the PVN upregulated tyrosine hydroxylase and dopamine‐β‐hydroxylase (DBH) expressions in the NTS, and elevated DBH immunoreactivity in the PVN. In summary, our findings indicate that increased BDNF expression in the PVN abolishes the hypotensive actions of NTS catecholaminergic neurons both under baseline conditions and during stress despite a significant upregulation of catecholamine biosynthesizing enzymes in the NTS. Heart rate is differentially regulated by NTS catecholaminergic neurons during baseline conditions and stress, but these actions are also reduced by elevated BDNF levels in the PVN.

Support or Funding Information

Supported by AHA 11SDG7560022 and UVM start‐up funds.