Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by progressive loss of dopaminergic neurons, which is mediated by mitochondrial dysfunction, apoptosis, oxidative stress, microglial activation and inflammatory response. DP generates motor and non-motor symptoms and its treatment is eminently symptomatic. The treatments begin with an effective pharmacological approach that evolves, negatively, generating extreme complications. At this stage, the gold standard of treatment is the deep brain stimulation (DBS) of the subthalamic nucleus (STN), which brings evident benefits to the motor and non-motor symptoms. In this project, we intend to demonstrate the relationship between prevention of mitochondrial dysfunction, inflammatory response and neuroplasticity control with the therapeutic effect of DBS-STN in an experimental model of PD. To this end, we will evaluate the effect of DBS-STN in rats with nigrostriatal lesion, induced by striatal 6-OHDA, on motor (rotation and immobility), nociceptive (hyperalgesia) and depression (forced swimming test) responses. We will evaluate the dopaminergic deficit by labeling for tyrosine hydroxylase in the substantia nigra (SN) and by apomorphine-induced rotation. Also, we will evaluate the mitochondrial dysfunction, neuronal pattern and glial activation as well as inflammasome and inflammatory response in the SN, striatum, globus pallidus and primary motor cortex, in the presence and absence of DBS-STN. We hypothesized that DBS will be able to modulate the mitochondrial dysfunction and consequently delaying neuronal death by modulating the inflammatory response in compromised areas in PD. With this work we intend to elucidate the mechanism of action of DBS, focusing on neuroinflammation, in order to guide the improvement of the therapeutic interventions for patients with PD.
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