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Role of opioids, cannabinoids, dopamine and neuroinflammation systems on pain threshold modulated by physical exercise in a rat Parkinson Disease model using a radioactive labeled substances

Grant number: 18/25204-1
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): June 05, 2019
Effective date (End): December 04, 2019
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Marucia Chacur
Grantee:Karina Henrique Binda
Supervisor abroad: Anne M Landau
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Aarhus University, Denmark  
Associated to the scholarship:17/26821-1 - Effect of physical exercise on induced nociception in the Parkinson's Disease model in rats, BP.MS

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease among elderly people, causing a large socioeconomic impact with increasing life expectancy of worldwide. In addition to motor symptoms, there is a high prevalence of pain symptoms which can be responsible for worsening patient's quality of life. Physical exercise, in turn, has already been described for its beneficial effects on PD with decreased neuronal loss in animal models, improved quality of life and pain symptoms of patients. In addition, recent data from our group revealed that physical exercise was able to decrease pain sensitivity, modulate the expression of opioid and cannabinoid receptors in the unilateral model of PD. Thus, this project will use a bio-analytical technique (autoradiography) to analyze specificity and sensitivity of radiotracers which can be useful for PET scan analysis, a good noninvasive tool for biological measurement. For this, we will evaluate the modulation of opioid (Mi) and cannabinoid (CB2) receptors, neuroinflammation (Activated microglia) and dopamine system (DAT, VMAT2 and D2/D3 receptors) with a complementary technique, autoradiography, through different radiotracers in different groups in regions of the nervous system involved with neural circuit of pain, being: periaqueductal gray (PAG) and anterior cingulate cortex (ACC). For receptors modulations analysis autoradiography techniques will be performed on a new, state-of-the-art ai4R Beaver/Beaquant system at Aarhus University, Denmark. The data will be collected from male rats submitted to PD like model, and to treadmill exercise protocol. Exercise will be performed 3 times per week for 40 minutes during 5 weeks at 10 m/min. Nociceptive behavior will be evaluated at 8 different moments, being: baseline (before induction of the model), 7, 14, 21, 28, 35, 42 and 49 days after the induction of the PD model. At the end of protocol experiments, animals will be euthanized 50 days after surgery to perform the autoradiography. Then with this technique and with this new system just acquired at the PET Center it will be possible to have a greater contribution to a better understanding of the results already obtained during the Master's degree and in the future possibly this will lead to a longstanding collaboration between the two laboratories and in vivo PET imaging can be conducted in future animal models and translated to patient.