Premium
BDNF shifts excitatory‐inhibitory balance in the paraventricular nucleus of the hypothalamus (PVN) to elevate blood pressure
Author(s) -
Thorsdottir Daniella,
Einwag Zachary D,
Erdos Benedek
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.744.4
Subject(s) - glutamatergic , endocrinology , medicine , chemistry , glutamate receptor , neuroscience , inhibitory postsynaptic potential , hypothalamus , excitatory postsynaptic potential , receptor , biology
The PVN is an important cardiovascular and autonomic center involved in sympathetic nerve activity and blood pressure (BP) regulation. Stimulation of PVN presympathetic neurons elevate sympathetic activity and BP via excitatory glutamatergic projections to the rostral ventrolateral medulla and the intermediolateral cell column of the spinal cord. Presympathetic neuronal activity is regulated by the balance of excitatory glutamatergic and inhibitory GABA‐ and noradrenergic signaling. BDNF is a neurotrophic factor capable of modulating glutamatergic, GABAergic and catecholaminergic (CA‐ergic) signaling in the CNS by changing expression and membrane trafficking of neurotransmitter receptors and transporters and by increasing the soma size of neurons. Within the PVN, BDNF expression is upregulated in response to physical and psychological stressors; therefore, BDNF may play a significant role in mediating stress‐induced changes in autonomic regulation of BP. Thus, we set out to examine the long‐term effects of BDNF overexpression within the PVN on NMDA‐, GABA A ‐ and adrenergic receptor‐mediated BP mechanisms and its effect on PVN neuronal soma size. To test this, Sprague Dawley (SD) rats received bilateral PVN injections of AAV2 viral vectors expressing either GFP or BDNF. Three weeks later, BP and heart rate (HR) responses to PVN injections of AP5 (10 mM), an NMDA antagonist, gabazine (2 mM), a GABA A receptor antagonist, and isoprenaline (250 μM), a non‐selective β‐adrenergic agonist, were recorded under alpha chloralosed‐urethane anesthesia. To test if BDNF alters the soma size of PVN neurons, fixed PVN brain sections were analyzed in ImageJ to quantify the soma size of BDNF or GFP expressing neurons. Our results showed that in the BDNF group, peak decreases in BP and HR in response to AP5 were −21±4 mmHg and − 38±13 BPM, compared with −2±1 mmHg (p<0.0001) and −3±1 BPM (p<0.0001) in the GFP group. In response to gabazine, peak increases in BP and HR in the BDNF group were 52±3 mmHg and 85±19 BPM, compared with 91±6 mmHg (p<0.01) and 20±3 BPM (p=0.06, n.s.) in the GFP group. In response to isoprenaline, peak decreases in BP and HR in the BDNF group were −8±1 mmHg and −19±12 BPM, compared with −35±2 mmHg (p<0.001) and −34±9 BPM (p=0.39, n.s.) in the GFP group. Analysis of PVN neuronal dimensions showed that the BDNF treated group had a significantly larger average soma size of 220±11 μm 2 compared to the GFP group of 122±6 μm 2 (p<0.0001). In summary, our findings indicate BDNF may alter the excitatory‐inhibitory balance in the PVN by enhancing glutamatergic and diminishing GABAergic and CA‐ergic signaling mechanisms within the PVN. In addition, BDNF‐induced increases in the volume and membrane surface area of PVN neurons could also contribute to long‐term changes in BP regulatory mechanisms. Support or Funding Information Supported by R01 HL133211‐01A1 and UVM start‐up funds. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .