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Parkinson's Disease and animal models of neuroprotection

Grant number: 09/52869-5
Support type:Regular Research Grants
Duration: December 01, 2009 - November 30, 2011
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:LUIZ ROBERTO GIORGETTI DE BRITTO
Grantee:LUIZ ROBERTO GIORGETTI DE BRITTO
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neurodegenerative diseases represent one of the most important challenges of the neurosciences. Parkinson's disease, for instance, affects millions of persons throughout the world, and these numbers are expected to double during the next 20 years. Therefore, Parkinson's disease has been the target of intense research aimed at understanding its etiology and at developing new treatment strategies. The main purpose of this study is to evaluate two possible neuroprotective processes in an animal Parkinson model, namely physical exercise and the application of cannabinoid agents. Wistar rats will receive intrastriatal injections of 6-hydroxydopamine, which retrogradely and selectively destroys cathecolaminergic neurons, and will be evaluated by means of behavioral tests and neuroanatomical procedures in order to ascertain the installation of the neuropathology. They will then be subjected to exercise protocols and administration of cannabinoid agents to verify their impact on the ensuing neurodegenerative processes. Behavioral analysis will be conducted with traditional rotational and open field tests, and the methods to evaluate the impact of the lesion and of the different treatments upon the nervous system will include histochemistry (Fluoro-Jade, TUNEL, and dihydroethidine) and immunohistochemistry/immunoblotting (for tyrosine hydroxylase, cannabinoid receptors, nitric oxide synthesizing enzymes, glial markers, caspases, AKT and ERK kinases, neurotrophins and enzymes that generate reactive oxygen species). This project may increase the knowledge of the effects of physical exercise and of the impact of the endocannabinoid system upon the neurodegenerative processes involved in Parkinson's disease, as a contribution to the future development of strategies aimed at reducing the level of cell death occurring in that condition. (AU)