Michael Salvatore, Ph.D.
Permanent URI for this communityhttps://hdl.handle.net/20.500.12503/31847
Member, Institute for Healthy Aging
Associate Professor, Pharmacology & Neuroscience
Email: Michael.Salvatore@unthsc.edu
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Browsing Michael Salvatore, Ph.D. by Subject "Humans"
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Item Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats(IOS Press, 2022-06-28) Salvatore, Michael F.; Soto, Isabel; Kasanga, Ella A.; James, Rachael; Shifflet, Marla K.; Doshier, Kirby; Little, Joel T.; John, Joshia; Alphonso, Helene M.; Cunningham, J. Thomas; Nejtek, Vicki A.BACKGROUND: Rodent Parkinson's disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient. OBJECTIVE: To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact. METHOD: We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr /=3 months, >/=3x/week. In 4-month-old Pink1 knockout (KO) rats exercising in a progressively-increased treadmill speed regimen, we determined a specific treadmill speed that increased HR to an extent similar in human subjects. RESULTS: After completing aerobic exercise for approximately 30 min, PD subjects had increased HR approximately 35% above baseline ( approximately 63% maximum HR). Motor and cognitive test results indicated the exercising subjects completed the timed up and go (TUG) and trail-making test (TMT-A) in significantly less time versus exercise-naive PD subjects. In KO and age-matched wild-type (WT) rats, treadmill speeds of 8-10 m/min increased HR up to 25% above baseline ( approximately 67% maximum HR), with no further increases up to 16 m/min. Exercised KO, but not WT, rats showed increased locomotor activity compared to an age-matched exercise-naive cohort at 5 months old. CONCLUSION: These proof-of-concept results indicate HR is a cross-species translation parameter to evaluate aerobic exercise impact on specific motor or cognitive functions in human subjects and rat PD models. Moreover, a moderate intensity exercise regimen is within the physical abilities of early-stage PD patients and is therefore applicable for interrogating neurobiological mechanisms in rat PD models.Item Is there a Neurobiological Rationale for the Utility of the Iowa Gambling Task in Parkinson's Disease?(IOS Press, 2021-04-13) Salvatore, Michael F.; Soto, Isabel; Alphonso, Helene M.; Cunningham, Rebecca L.; James, Rachael; Nejtek, Vicki A.Up to 23% of newly diagnosed, non-demented, Parkinson's disease (PD) patients experience deficits in executive functioning (EF). In fact, EF deficits may occur up to 39-months prior to the onset of motor decline. Optimal EF requires working memory, attention, cognitive flexibility, and response inhibition underlying appropriate decision-making. The capacity for making strategic decisions requires inhibiting imprudent decisions and are associated with noradrenergic and dopaminergic signaling in prefrontal and orbitofrontal cortex. Catecholaminergic dysfunction and the loss of noradrenergic and dopaminergic cell bodies early in PD progression in the aforementioned cortical areas likely contribute to EF deficits resulting in non-strategic decision-making. Thus, detecting these deficits early in the disease process could help identify a significant portion of individuals with PD pathology (14-60%) before frank motor impairment. A task to evaluate EF in the domain of non-strategic decision-making might be useful to indicate the moderate loss of catecholamines that occurs early in PD pathology prior to motor decline and cognitive impairment. In this review, we focus on the potential utility of the Iowa Gambling Task (IGT) for this purpose, given significant overlap between in loss of dopaminergic and noradrenergic cells bodies in early PD and the deficits in catecholamine function associated with decreased EF. As such, given the loss of catecholamines already well-underway after PD diagnosis, we evaluate the potential utility of the IGT to identify the risk of therapeutic non-compliance and a potential companion approach to detect PD in premotor stages.