CONSEQUENCES OF DOPAMINERGIC AGONIST ASSOCIATED WITH BDNF TREATMENT ON BEHAVIORAL ALTERATIONS AND CYTOLOGICAL CHANGES IN AN EXPERIMENTAL MODEL OF PARKINSON DISEASE DUE TO MANGANESE EXPOSURE

Parkinson disease (PD) is characterized by dopaminergic (DA) neuronal loss and motor alterations; in this way, an effective therapy should protect and regenerate the DA neurons and striatal innervation. Brain-derived neurotrophic factor (BDNF) is a cell survival mediator and can improve neuronal death, and the activation of DA D3 receptors seems to protect the DA neurons. Thus, there is a synergistic relationship between BDNF and D3 receptors; which would be a neuroprotective therapy. PD animal models, although exhibit some of the features, no one mimics the alterations observed in the disease. PD-Manganese (Mn) inhalation model was used in this report since it is bilateral, non-invasive and progressive. The rats were exposed to Mn 1 hour 3 times a week, and the motor tests were conducted to measure the performance as well as the progressive damage at 3 and 6 months of exposure. Subsequently, the D3 agonist treatment (7-OH-DPAT) and BDNF gene transfection to DA neurons were co-administered, and then we evaluated its effect measuring the animals' performance, and if the recovery was associated with DA neuronal and striatal dendritic spines preservation. The results showed that the animals presented PD-like motor alterations, and great DA neurons and striatal dendritic spines loss. The behavior recovery was associated with the DA neurons recuperation and with the number of dendritic spines of the striatal neurons. Thus, the BDNF overexpression in DA neurons related to the D3 receptors activation seems to be a promising approach for restoring motor alterations and DA neurons in PD.