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Investigation into neural and muscular components of breathing in Down Syndrome

Award Number: R15HD076379
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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Investigation into neural and muscular components of breathing in Down Syndrome - DESCRIPTION (provided by applicant): Down syndrome (Ds) is the most common chromosomal cause of intellectual disability that results from triplication of chromosome 21 genes. Persons with Ds demonstrate cognitive deficits in addition to co- morbidities that often accompany Ds, including cardiovascular abnormalities, thyroid disease, obesity, hypotonia and muscle weakness, upper airway obstructions, and sleep apnea. Although sleep apnea is a prevalent disorder in children and adults with Ds, the mechanisms responsible for these breathing deficits have not been elucidated. Our preliminary data reveal attenuated minute ventilation and mean inspiratory flow, and an increased number of apneas in Ts65Dn mice, a model of Ds; suggestive of ventilation deficits that may have a neural origin. Preliminary data also suggest impaired force production of diaphragm muscle from Ts65Dn mice in response to fatiguing muscle contractions. Together, these data suggest that the altered breathing patterns observed in Ts65Dn mice could be derived from neural and muscular origins. The experiments described in this proposal will further examine neural and diaphragm muscle contributions to breathing alterations in Ts65Dn mice and examine the activity of the proteasome, a major cellular proteolytic system, in the C3-C5 region of the spinal cord as a potential mechanism of breathing alterations. Aim #1 will characterize conscious ventilation in Ts65Dn mice. We will further characterize differences in the breathing pattern of Ts65Dn mice and reveal if arterial partial pressures of CO2 are elevated in conscious Ts65Dn mice vs. colony controls. Aim #2 will determine if breathing deficits of Ts65Dn mice are associated with reduced neural output of the phrenic nerve. These experiments will quantify the phrenic burst amplitude to measure the neural contribution to breathing. We will also assess proteasome activity of the phrenic nucleus to test the hypothesis that proteasome activity will be lower in Ts65Dn mice. Aim #3 will assess diaphragm muscle function in Ts65Dn mice. These experiments will determine if diaphragm from Ts65Dn mice exhibits increased susceptibility to fatigue in vitro compared to diaphragm from colony controls. All aims will study mice at 3 months, 12 months and 18 months of age to further describe aging in this model. Since individuals with Ds demonstrate characteristics of accelerated aging it will be important to know how ventilation changes with advancing age in Ts65Dn mice. Overall, this project will provide insight into the physiological systems that modulate breathing in Ds with the objective of improving the quality of life of persons with this condition. These experiments will support the sciences at Le Moyne College and engage undergraduate students in biomedical research to train the next generation of researchers.


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: 2022 ( Subtotal = $3,267 )
2022	2018	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	10/22/2021	SUPPLEMENT FOR EXPANSION	$3,267
2022	2016	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	001	1	12/22/2021	NEW	$0
														Subtotal = $3,267

Issue Date FY: 2021 ( Subtotal = -$3,267 )
2021	2018	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	9/7/2021	SUPPLEMENT FOR EXPANSION	-$3,267
														Subtotal = -$3,267

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2016	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	8/14/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $18,624 )
2018	2018	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	8/22/2018	SUPPLEMENT FOR EXPANSION	$18,624
														Subtotal = $18,624

Issue Date FY: 2017 ( Subtotal = $209,313 )
2017	2017	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	7/21/2017	SUPPLEMENT FOR EXPANSION	$203,313
2017	2016	LE MOYNE COLLEGE	1419 SALT SPRINGS RD	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	001	1	9/5/2017	NEW	$6,000
														Subtotal = $209,313

Issue Date FY: 2016 ( Subtotal = $363,000 )
2016	2016	LE MOYNE COLLEGE	LE MOYNE HEIGHTS	SYRACUSE	NY	13214	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	8/31/2016	NEW	$363,000
														Subtotal = $363,000

Grand Total All Awards = $590,937

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Investigation into neural and muscular components of breathing in Down Syndrome

Award Number: R15HD076379

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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