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Role of PVN neuropeptide projections to the nTS in cardiorespiratory control

Award Number: F31HL140858
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/11/2017
PERIOD OF PERFORMANCE END DATE: 06/01/2019

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Role of PVN neuropeptide projections to the nTS in cardiorespiratory control - Statement of Problem: The arterial chemoreflex is an essential protective mechanism for adaptive responses to hypoxia (Hx). However, chemoreflex dysfunction, including over-excitation of chemoreflex pathways leads to respiratory instability, increased sympathetic nerve activity (SNA) and hypertension in disease states, including heart failure and hypertension. Information regarding mechanisms of action in the chemoreflex neurocircuitry is lacking. The neuropeptide neurons CRH and OT neurons in the paraventricular nucleus of the hypothalamus (PVN) may influence sympathoexcitatory and respiratory control via projections to brainstem cardiorespiratory nuclei. Previous studies indicate that CRH increases cardiorespiratory function in both healthy subjects and elderly patients dependent on artificial respiration, suggesting that CRH may offer therapeutic potential in various disease states that display chemoreflex dysfunction. However, the central mechanisms by which PVN neuropeptide neurons contribute to these responses are unclear. Specific Aims: Aim 1: To determine the contribution of PVN CRH neurons to cardiorespiratory control at baseline and in response to peripheral chemoreflex stimulation Aim 2: To determine the contribution of PVN OT neurons to cardiorespiratory control, and examine central interactions between CRH and OT in the nTS Experimental Approach: The overall Hypothesis of this project is that PVN CRH neurons that project to the nTS enhance cardiorespiratory responses to chemoreflex stimulation via activation of nTS CRH receptors and OTergic mechanisms. Aim 1 will determine the extent to which PVN CRH neurons contribute to cardiorespiratory output at baseline and during peripheral chemoreflex stimulation via projections to the nTS. Aim 2 will determine the extent to which PVN CRH and OT neurons modulate cardiorespiratory responses to chemoreflex via interactions within the nTS. Significance of Results: The long-term objectives of this study are to further characterize interactions between the PVN and the nTS, and the mechanisms by which this reciprocal pathway shapes cardiorespiratory responses to peripheral chemoreflex stimulation. Determining the pathways, circuits and mechanism(s) mediating chemoreflex function and how these may be changed in disease would be of great benefit in designing rational and targeted therapeutic approaches in these debilitating diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = -$2,326 )
2021	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	000	2	1/21/2021	NON-COMPETING CONTINUATION	-$2,326
														Subtotal = -$2,326

Issue Date FY: 2020 ( Subtotal = -$13,273 )
2020	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	000	2	11/27/2019	NON-COMPETING CONTINUATION	-$13,273
														Subtotal = -$13,273

Issue Date FY: 2019 ( Subtotal = $29,962 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	000	2	12/13/2018	NON-COMPETING CONTINUATION	$29,962
														Subtotal = $29,962

Issue Date FY: 2018 ( Subtotal = $29,943 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	002	1	8/2/2018	NEW	$480
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	001	1	12/11/2017	NEW	$0
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cardiovascular Diseases Research	000	1	12/11/2017	NEW	$29,463
														Subtotal = $29,943

Grand Total All Awards = $44,306

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Role of PVN neuropeptide projections to the nTS in cardiorespiratory control

Award Number: F31HL140858

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/11/2017

PERIOD OF PERFORMANCE END DATE: 06/01/2019

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