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Subthalamic stimulation and serotoninergic modulation in a Parkinsons Disease rat model

Grant number: 19/27643-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2020
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rosana de Lima Pagano
Grantee:Gustavo Pires Mauricio
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disease that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons. PD includes motor and non-motor symptoms, and pain is one of the most prevalent, debilitating and poorly understood non-motor symptoms. The treatment of PD is eminently symptomatic, starting with an effective pharmacological approach that loses its effect over time, generating several complications. In this phase, the gold standard of treatment is the Deep Brain Stimulation (DBS) of the subthalamic nucleus (NST), which has clear benefits in relation to the motor and non-motor symptoms of PD. It was observed by our group that DBS-NST induces evident motor improvement and reduces hypernociception in hemiparkinsonian rats, a response accompanied by reversal of dopaminergic motor pathway neuroinflammation and reversal of neuronal and glial hyperactivation in the posterior spinal cord (CPME). Considering the importance of serotonin in controlling nociceptive response, in this project we will investigate the effect of DBS-NST on the serotoninergic system of hemiparkinsonian rats. To this end, we will evaluate serotonin expression in different areas involved with nociceptive response control. We hypothesized that DBS-NST is capable of reversing, in hyparkinsonian rats, excess serotonin in limbic areas and serotoninergic deficit in the descending analgesic pathway. With this work we intend to elucidate part of the mechanism of action of DBS in non-motor symptoms, focusing on pain, in order to guide the improvement of more effective and less invasive therapeutic interventions for PD patients. (AU)