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The impact of aging on the functional and anatomical coupling between brainstem noradrenergic neurons and upper airway muscles

Award Number: R01AG065233
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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The impact of aging on the functional and anatomical coupling between brainstem noradrenergic neurons and upper airway muscles - Abstract Obstructive sleep apnea (OSA) is a growing sleep-related breathing disorder with the prevalence rate of 10-15% in the middle-age adults and of 32%-62% in elderly. OSA patients undergo recurrent upper airway collapse due to suppression of activity of upper airway dilator muscles during sleep, which causes repeated hypoxia, frequent stressful arousals and sleep deprivation. OSA has a major health impact due to its association with cardiovascular, metabolic and neurocognitive morbidities, including a risk factor for developing Alzheimer’s disease and increased mortality in older adults. Brainstem noradrenergic (NA) system plays an important role in maintaining the tonus of upper airway (UA) muscles to keep airway open during wakefulness. Therefore, the decrease of NA release during sleep largely contributes to a loss of the UA muscle tone at night, which is a major neurological cause of OSA. Studies suggest that aging has a detrimental effect on the NA system. However, there is little information regarding age-related changes in the control of UA muscles by brainstem NA neurons, which may be a basis of the increased prevalence of OSA in older population. In the proposed project, we will use a novel molecular-genetic approach that will allow a cell-type-specific activation of NA neurons in the brainstem A1/C1, A5, A7 and SubCorelueus (SubC) nuclei while recording activity of the genioglossus (GG), a major UA dilator muscle, during natural sleep and wakefulness in young (3- 4 months) and old (16-20 months) behaving DBH-Cre mice. We will determine the age-related changes in 1) the ability of A1/C1, A5, A7 and SubC neurons to activate the GG muscle; 2) the contribution of A1/C1, A5, A7 and SubC neurons to depression of the GG muscle activity during NREM sleep and REM sleep; 3) the number of NA neurons in these and other brainstem NA nuclei; and 4) the density of axons and their terminals that originate from A1/C1, A5, A7 and SubC neurons and project to hypoglossal and other UA motoneurons. The proposed work will reveal neurological bases of the reduction in effectiveness of UA muscles to maintain UA open during sleep in older individuals. The results of this study will fill a major gap in our understanding of underlying mechanisms of OSA pathogenesis in elderly and lay the groundwork for translational research of OSA pathology in aging to develop preventive and/or therapeutic strategies for clinical management of OSA in older patients.


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: 2024 ( Subtotal = $490,158 )
2024	2024	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Aging Research	002	6	8/13/2024	SUPPLEMENT FOR EXPANSION	$156,008
2024	2024	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	6	3/5/2024	NON-COMPETING CONTINUATION	$300,735
2024	2024	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Aging Research	001	6	6/28/2024	NON-COMPETING CONTINUATION	$33,415
														Subtotal = $490,158

Issue Date FY: 2023 ( Subtotal = $334,150 )
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	5	2/27/2023	NON-COMPETING CONTINUATION	$334,150
														Subtotal = $334,150

Issue Date FY: 2022 ( Subtotal = $334,150 )
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	000	4	4/25/2022	NON-COMPETING CONTINUATION	$334,150
														Subtotal = $334,150

Issue Date FY: 2021 ( Subtotal = $334,150 )
2021	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	003	3	6/22/2021	NON-COMPETING CONTINUATION	$334,150
2021	2020	BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE, INC.	11301 WILSHIRE BLVD BLDG 114 RM 218	LOS ANGELES	CA	90073	LOS ANGELES	USA	Aging Research	000	1	11/11/2020	NEW	-$281,055
2021	2020	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	001	2	11/12/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$281,055
2021	2020	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Aging Research	002	2	5/24/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $334,150

Issue Date FY: 2020 ( Subtotal = $281,055 )
2020	2020	BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE, INC.	11301 WILSHIRE BLVD BLDG 114 RM 218	LOS ANGELES	CA	90073	LOS ANGELES	USA	Aging Research	000	1	4/21/2020	NEW	$281,055
														Subtotal = $281,055

Grand Total All Awards = $1,773,663

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The impact of aging on the functional and anatomical coupling between brainstem noradrenergic neurons and upper airway muscles

Award Number: R01AG065233

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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