PET imaging of dopamine synthesis and neuroinflammation to evaluate the exercise-induced reduction in dopaminergic damage in a rat model of PD

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. 20% of patients diagnosed with PD are discovered false-diagnosed after post mortem examination. Thus, it would be of great importance to develop techniques to accurately diagnose the disease in all stages in vivo. Positron emission tomography (PET) is a very effective diagnostic tool for noninvasive imaging of metabolic or functional disorders in target tissues. Exercise, in turn, has been described in terms of its beneficial effects in PD with decreased neuronal loss and improvement of behavioral, being able to act as a therapeutic strategy for the disease. The objective of this project is analyze the effectiveness of PET markers, dopaminergic ([18F]FDOPA) system and neuroinflammation ([11C] PK11195) responses, as an assessment of the beneficial effects promoted by exercise. To do this, we will correlate the histological changes of rat tissue with neurofunctional image (a possible procedure at the clinical level) and behavioral tests. The rats will be subjected to the model of PD induced by unilateral striatal 6-hydroxydopamine and to a protocol of intermittent treadmill exercise. 5 days before, and 8 and 30 days after the PD induction the rats will be submitted to the PET protocol. The behavioral responses of rats will be investigated with open field, object recognition, rotarod test and cylinder test before the PET protocol. Immunostaining will be used to assess microglial activation with ionized calcium-binding adapter molecule 1 (Iba-1), and the dopaminergic system will be tasted with tyrosine hydroxylase (TH). Thus, this study may provide a pre-clinical test for [18F]FDOPA and [11C] PK11195 PET markers and correlate neuroimaging with beneficial cellular events of physical exercise in the PD. (AU)