PATHOPHYSIOLOGICAL MECHANISMS AND NEUROPROTECTIVE INTERVENTIONS IN A PROGRESSIVE ANIMAL MODEL OF PARKINSON'S DISEASE

Abstract

Parkinson´s disease is the second most prevalent age-related neurodegenerative disorder. The main symptoms of this pathology are severe motor deficits, but non-motor signs are also present. The pathophysiology comprises a progressive neuronal loss, and there is currently no effective intervention for slowing the degeneration. There is evidence of an important role of neuronal oxidative stress, inflammation processes and ±-synuclein accumulation in the mechanisms leading to degeneration, which affects mostly dopaminergic neurons. This highlights the importance of the investigation of neuroprotective strategies. Currently used animal models of PD present limitations regarding the investigation of possible neuroprotective treatments. In general, the models involve neurotoxins that leads to immediate severe motor impairment, precluding the evaluation of possible delays in the symptoms progression. We have recently validated a protocol for the study of PD symptoms progression: the repeated treatment with a low dose of reserpine (RES, a vesicular monoamine transporter inhibitor). At high doses, RES induces immediate motor damage. The repeated administration of a ten times lower dose produces progressive motor deficits and non-motor symptoms, together with oxidative damage and reduction in tyrosine hydroxylase. Although this protocol has great potential for the study of PD, it is necessary to better characterize some pathophysiological aspects compatible to the human condition. Our goals are: 1- to extend the validation of the progressive RES model of PD by the investigation of inflammation, neuronal death and ±-synuclein levels parameters and 2- to investigate the effects of classical antioxidants and a natural product with antioxidant potential on the development of the behavioral and neuronal alterations in rats subjected to the progressive RES model of DP. The results will be compared to the effects of these neuroprotective attempts in conventional acute models. (AU)