BDNF shifts excitatory-inhibitory balance in the paraventricular nucleus of the hypothalamus (PVN) to elevate blood pressure
Conference Year
January 2019
Abstract
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-, GABAA- 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 GABAA 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 (p2 compared to the GFP group of 122±6 µm2 (p
Primary Faculty Mentor Name
Benedek Erdos
Faculty/Staff Collaborators
Zachary D. Einwag (Lab Technician)
Status
Graduate
Student College
Graduate College
Program/Major
Neuroscience
Primary Research Category
Biological Sciences
BDNF shifts excitatory-inhibitory balance in the paraventricular nucleus of the hypothalamus (PVN) to elevate blood pressure
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-, GABAA- 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 GABAA 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 (p2 compared to the GFP group of 122±6 µm2 (p