There is an overwhelming body of evidence that links sarcopenia, the age-related changes in muscle size, strength, and function, to anatomical and physiological changes within motoneurons, nerve-muscle connections, and the muscles themselves. In addition to skeletal muscle in the limbs, age-related changes undoubtedly occur in cranial muscles and the brainstem neurons that innervate them. Alterations in tongue muscle and hypoglossal motoneuron structure and function may contribute to the age-related decline in swallowing and speech. However, little is known about the pathophysiology underlying age-related changes in the cranial neuromuscular system. In our laboratories, we have found age-related changes in tongue muscles, the neuromuscular junction (NMJ), and in hypoglossal motoneurons and their serotonergic neuromodulatory inputs in a rodent model. In the proposed research, we plan to use a progressive resistance tongue exercise program we have developed in awake rats to investigate the role of exercise in preventing or reversing age-related changes within the tongue and hypoglossal nucleus. Our hypothesis is that age-associated changes in the hypoglossal nucleus, together with denervation-reinnervation processes, are major contributors to lingual sarcopenia, and that these processes can be prevented or reversed by exercise. We will test this hypothesis by comparing physiological, morphological, biochemical, and molecular parameters of tongue muscles and hypoglossal motoneurons in young, middle-aged, and old rats that have undergone behavioral tongue exercise versus those in a sham-exercise control group. The proposed research has 5 specific aims. In young, middle-aged and old rats, we will determine: (1) the degree to which behavioral tongue forces and muscle contractile properties change as a function of age and exercise, and morphological, biochemical, and molecular variables that are predictive of changes in tongue muscle contractile properties;(2) the effect of age and exercise on morphological and biochemical properties of tongue muscles;(3) the effect of age and exercise on morphology of nerve-muscle connections, (4) the effect of age and exercise on neuronal plasticity in the hypoglossal nucleus;and, (5) the role of neurotrophins in exercise- induced neuronal plasticity in young, middle-aged, and old rats. This work is innovative and important because the mechanisms by which exercise may impact neuroprotective effects in the lingual motor system are largely unexplored. Our neuromuscular model is the first to evaluate the effects of a behavioral exercise program on cranial motoneurons and tongue physiology. Further, this work is highly significant in providing a basis for understanding mechanisms underlying the putative benefits of exercise as a therapeutic intervention for age-related changes in cranial muscles.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008149-05
Application #
7991353
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2006-12-05
Project End
2013-06-30
Budget Start
2010-12-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$295,463
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Pultorak, Joshua D; Kelm-Nelson, Cynthia A; Holt, Lauren R et al. (2016) Decreased approach behavior and nucleus accumbens immediate early gene expression in response to Parkinsonian ultrasonic vocalizations in rats. Soc Neurosci 11:365-79
Schaser, Allison J; Ciucci, Michelle R; Connor, Nadine P (2016) Cross-activation and detraining effects of tongue exercise in aged rats. Behav Brain Res 297:285-96
Kletzien, Heidi; Russell, John A; Connor, Nadine P (2016) The effects of treadmill running on aging laryngeal muscle structure. Laryngoscope 126:672-7
Kelm-Nelson, Cynthia A; Yang, Katie M; Ciucci, Michelle R (2015) Exercise Effects on Early Vocal Ultrasonic Communication Dysfunction in a PINK1 Knockout Model of Parkinson's Disease. J Parkinsons Dis 5:749-63
Becker, Benjamin J; Russell, John A; Connor, Nadine P (2015) Effects of aging on evoked retrusive tongue actions. Arch Oral Biol 60:966-71
Sandage, Mary J; Connor, Nadine P; Pascoe, David D (2014) Vocal function and upper airway thermoregulation in five different environmental conditions. J Speech Lang Hear Res 57:16-25
Russell, John A; Connor, Nadine P (2014) Effects of age and radiation treatment on function of extrinsic tongue muscles. Radiat Oncol 9:254
Ciucci, Michelle R; Schaser, Allison J; Russell, John A (2013) Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease. Behav Brain Res 252:239-45
Connor, Nadine P; Russell, John A; Jackson, Michelle A et al. (2013) Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats. Muscle Nerve 47:230-40
Sandage, Mary J; Connor, Nadine P; Pascoe, David D (2013) Voice function differences following resting breathing versus submaximal exercise. J Voice 27:572-8

Showing the most recent 10 out of 33 publications