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Impact of nigral and extranigral neurodegeneration on aerodigestive discoordination in a pesticide model of Parkinson's disease

Award Number: R01ES035118
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Impact of nigral and extranigral neurodegeneration on aerodigestive discoordination in a pesticide model of Parkinson's disease - Project summary Swallowing problems in Parkinson’s disease (PD) affect 90% of patients, with significant consequences for quality of life and morbidity, and are resistant to current dopamine deficiency targeting treatments for movement impairments caused by PD (Coelho et al., 2010; Plowman-Prine et al., 2009). The treatment resistant nature of swallowing problems implicates neurological damage outside the substantia nigra and striatum. Most cases of PD result in part from exposure to toxic substances, resulting in widespread brain pathologies (de Lau & Breteler, 2006). PD affects multiple components of feeding and their coordination, which are controlled by different parts of the brain (Kwon &Lee, 2019). The overall goal of this project is to identify treatment resistant components of feeding and their neuropathological correlates in PD. The central hypothesis is that specific components of the feeding process are differentially impaired by neurodegeneration inside and outside the substantia nigra resulting in an overall treatment resistant phenotype. Three related specific aims will test this hypothesis. Specific aims 1 will compare behavioral, biomechanical, and neuromuscular differences in chew-swallow-breathe coordination in a generalized model of PD, the rat rotenone injection model (Cannon et al., 2009) versus a 6-OHDA induced targeted nigrostriatal lesion model (Russell et al., 2013) to identify feeding dysfunction not related to nigrostriatal deficits. Specific aim two will examine how differences in behavioral and sensorimotor complexity between solid food eating and liquid drinking affect severity of behavioral, biomechanical, and neuromuscular oropharyngeal discoordination in a rotenone injection rat model of PD. Specific aim 3 will test the behavioral, biomechanical, and neuromuscular impact of levodopa-induced rescue of chewing function (Karlsson et al., 1992) on feeding coordination in a rotenone injection rat model of PD to identify pathophysiological mechanisms of dysphagia that are resistant to treatments targeting dopamine deficiency. The approach is innovative in combining complimentary lesion models, behavioral models, and neuropharmacological approaches, with a detailed analysis of feeding to find the pathophysiological basis of dysphagia treatment resistance in PD. The approach is significant in targeting the underlying mechanism of treatment resistance in a common, understudied symptom of PD. The neuromuscular, neuropathological, and biomechanical findings of this from this work will lead to further research into the neurological basis of treatment resistance of dysphagia in PD, with the ultimate goal of developing targeted therapeutic interventions.


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: 2026 ( Subtotal = $321,589 )
2026	2026	RU SCHOOL OF OSTEOPATHIC MEDICINE	42 E LAUREL RD	STRATFORD	NJ	08084	CAMDEN	USA	Environmental Health	000	3	6/15/2026	NON-COMPETING CONTINUATION	$321,589
														Subtotal = $321,589

Issue Date FY: 2025 ( Subtotal = $318,438 )
2025	2025	RU SCHOOL OF OSTEOPATHIC MEDICINE	42 E LAUREL RD	STRATFORD	NJ	08084	CAMDEN	USA	Environmental Health	000	2	6/27/2025	NON-COMPETING CONTINUATION	$318,438
														Subtotal = $318,438

Issue Date FY: 2024 ( Subtotal = $390,823 )
2024	2024	RU SCHOOL OF OSTEOPATHIC MEDICINE	42 E LAUREL RD	STRATFORD	NJ	08084	CAMDEN	USA	Environmental Health	000	1	8/23/2024	NEW	$390,823
														Subtotal = $390,823

Grand Total All Awards = $1,030,850

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Impact of nigral and extranigral neurodegeneration on aerodigestive discoordination in a pesticide model of Parkinson's disease

Award Number: R01ES035118

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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