Correlation of cellular, molecular, behavioral and neurofunctional parameters in Parkinson’s Disease with physical exercise in an animal model and in human postmortem tissue

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. PD promotes motor disorders. Exercise, in turn, has been described in terms of its beneficial effects in PD with decreased neuronal loss, improvement of behavioral and changes in the pattern of cortical excitability. The objective of this project is to understand physical exercise as a possible way to slow or reverse the motor abnormalities of PD, correlating the histological changes of rat tissue and postmortem human tissue (provided by the Faculty of Medicine, University of São Paulo) with neurofunctional image (a possible procedure at the clinic) and behavioral tests. To do this, we will evaluate neurochemical, neurofunctional and behavioral changes in rats and humans. The rats will be subjected to the model of PD induced by unilateral striatal 6-hydroxydopamine and to a protocol of treadmill exercise, and an analysis will be performed on postmortem human tissue The behavioral responses of rats will be investigated with apomorphine-induced rotational test and open field; human data will be correlated with target questionnaires of family or caregivers. Cellular and microglial activation will be determined by immunostaining for Egr-1 and Iba-1, respectively. By immunohistochemistry and immunoblotting, we will evaluate GFAP, synaptic proteins (synapsin and synaptophysin) and structural (neurofilaments and MAP- 2), and also dopamine receptors (D1 and D2) and BDNF (TrkB and p75) in different brain regions. Pathophysiological changes will be imaged in rats with the radiopharmaceuticals [11C] PK11195 PET (neuroinflammation) and 99mTc - TRODAT SPECT (dopaminergic system). We will also conduct in vitro autoradiography for [11C] PK11195 and 99mTc - TRODAT in histological sections of rat brain and human postmortem tissue. Thus, this study may provide a clinic correlation with cellular, molecular and neurofunctional events of PD with the effects of physical exercise. (AU)