Posted December 23, 2022

Dr. Michael Salvatore, University of North Texas Health Science Center

Dr. Michael Salvatore (University of North Texas Health Science Center [UNTHSC]) received an award from the Congressionally Directed Medical Research Programs’ Neurotoxin Exposure Treatment Parkinson’s (NETP) program to investigate the neurobiological mechanisms of exercise in two animal models of Parkinson’s disease (PD). Dr. Salvatore’s project is titled “Increasing Nigral Tyrosine Hydroxylase Expression as a Mechanism of Exercise-Mediated Recovery: Evaluation in Toxin and Rat Parkinson's Disease Genetic Models.”

The work aims to determine molecular pathways affected by exercise and specific intervention points in the molecular pathways to develop new treatments for PD. Specifically, Dr. Salvatore and colleagues, Dr. Christopher Bishop at Binghamton University, Dr. Jason Richardson at the Florida International University, and Dr. Vicki Nejtek, are looking at the neurobiological mechanisms of exercise impact, with special focus on changes in the substantia nigra. They are investigating whether these molecules act as regulators to mediate recovery of motor function related to exercise in PD. They will use two animal models for the investigation, a toxin-based model (the 6-OHDA rat model) and a genetic model (a Pink1 knockout model). Dr. Salvatore and Dr. Nejtek, along with Dr. Tom Cunningham at UNTHSC, recently found that a moderate-intensity aerobic exercise regimen can improve motor function in early-stage PD patients, a finding likely to increase the translation of results found in the rodent models. Moreover, the exercise-experienced Pink1 knockout rat also showed evidence of similar improvement in motor function compared to the exercise-naïve Pink1 knockout rat. In their recently published manuscript, the team also reported a treadmill speed that can be applied to rat PD models producing a similar intensity of aerobic exercise that yielded positive results in the PD patient.

The team is now investigating if this same intensity of aerobic exercise will produce the expected changes in dopamine regulation, at multiple levels of neurotransmission, in the substantia nigra. Outcomes to date suggest the alleviation of parkinsonian signs are not related to changes in the striatum, thus increasing the probability that increased dopamine function in the substantial nigra may drive these improvements. The research is indicating this is plausible since dopamine and tyrosine hydroxylase loss are more severe in the striatum than in substantia nigra when the exercise regimen begins.

Publication:
Salvatore MF, Kasanga EA, Soto I, John J, James RN, Doshier K, McElory CM, Shifflet MK, Little JT, Cunningham JT, and Nejtek VA. 2022. Establishing equivalent aerobic exercise parameters between early-stage Parkinson’s disease and Pink1 knockout rats. Journal of Parkinson’s Disease. In press.

Links:
Public and Technical Abstracts: Increasing nigral tyrosine hydroxylase expression as a mechanism of exercise-mediated recovery: Evaluation in toxin and rat Parkinson's disease genetic models

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