Correlation of cellular, molecular, behavioral and neurofunctional parameters in Parkinson’s Disease with physical exercise in an animal model and in human postmortem tissue

• Grant number: 13/25049-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2014
• Effective date (End): October 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Caroline Cristiano Real Gregório
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 14/23509-9 - PET imaging of dopamine synthesis and neuroinflammation to evaluate the exercise-induced reduction in dopaminergic damage in a rat model of PD, BE.EP.PD

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. PD promotes motor disorders. Exercise, in turn, has been described in terms of its beneficial effects in PD with decreased neuronal loss, improvement of behavioral and changes in the pattern of cortical excitability. The objective of this project is to understand physical exercise as a possible way to slow or reverse the motor abnormalities of PD, correlating the histological changes of rat tissue and postmortem human tissue (provided by the Faculty of Medicine, University of São Paulo) with neurofunctional image (a possible procedure at the clinic) and behavioral tests. To do this, we will evaluate neurochemical, neurofunctional and behavioral changes in rats and humans. The rats will be subjected to the model of PD induced by unilateral striatal 6-hydroxydopamine and to a protocol of treadmill exercise, and an analysis will be performed on postmortem human tissue The behavioral responses of rats will be investigated with apomorphine-induced rotational test and open field; human data will be correlated with target questionnaires of family or caregivers. Cellular and microglial activation will be determined by immunostaining for Egr-1 and Iba-1, respectively. By immunohistochemistry and immunoblotting, we will evaluate GFAP, synaptic proteins (synapsin and synaptophysin) and structural (neurofilaments and MAP- 2), and also dopamine receptors (D1 and D2) and BDNF (TrkB and p75) in different brain regions. Pathophysiological changes will be imaged in rats with the radiopharmaceuticals [11C] PK11195 PET (neuroinflammation) and 99mTc - TRODAT SPECT (dopaminergic system). We will also conduct in vitro autoradiography for [11C] PK11195 and 99mTc - TRODAT in histological sections of rat brain and human postmortem tissue. Thus, this study may provide a clinic correlation with cellular, molecular and neurofunctional events of PD with the effects of physical exercise. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOARES GUTIERREZ, RITA MARA; REAL, CAROLINE CRISTIANO; SCARANZI, CATHARINE RANIERI; GARCIA, PRISCILA CRESPO; OLIVEIRA, DALTON LUSTOSA; BRITTO, LUIZ ROBERTO; PIRES, RAQUEL SIMONI. Motor improvement requires an increase in presynaptic protein expression and depends on exercise type and age. Experimental Gerontology, v. 113, p. 18-28, NOV 2018. (13/25049-2)

CAROLINE CRISTIANO REAL; CLÁUDIA KIMIE SUEMOTO; KARINA HENRIQUE BINDA; LEA TENENHOLZ GRINBERG; CARLOS AUGUSTO PASQUALUCCI; WILSON JACOB FILHO; RENATA ELOAH DE LUCENA FERRETTI-REBUSTINI; RICARDO NITRINI; RENATA ELAINE PARAIZO LEITE; LUIZ ROBERTO DE BRITTO. O ESTILO DE VIDA ATIVO MELHORA O PERFIL DE EXPRESSÃO DE PROTEÍNAS EM INDIVÍDUOS COM A PATOLOGIA DE CORPOS DE LEWY. Dement. Neuropsychol., v. 15, n. 1, p. 41-50, 2021-04-09. (16/16166-3, 13/25049-2, 12/50329-6)

REAL, CAROLINE C.; GARCIA, PRISCILA C.; BRITTO, LUIZ R. G.; PIRES, RAQUEL S.. Different protocols of treadmill exercise induce distinct neuroplastic effects in rat brain motor areas. Brain Research, v. 1624, p. 188-198, OCT 22 2015. (11/18161-5, 13/25049-2)

GUIMARAES MARQUES, MARCIA JONATHAS; REAL, CAROLINE CRISTIANO; VICTORINO, DANIELLA BALDUINO; BRITTO, LUIZ ROBERTO; CAVALHEIRO, ESPER ABRAO; SCORZA, FULVIO ALEXANDRE; FERRAZ, HENRIQUE BALLALAI; SCORZA, CARLA ALESSANDRA. Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys. Neuroscience Letters, v. 709, SEP 14 2019. (16/17746-3, 13/25049-2, 16/06879-2, 12/50329-6)

CARVALHO, ROBERT H. F.; REAL, CAROLINE C.; CININI, SIMONE; GARCEZ, ALEXANDRE T.; DURAN, FABIO L. S.; MARQUES, FABIO L. N.; MELLO, LUIZ EUGENIO; BUSATTO FILHO, GERALDO; DE VRIES, ERIK F. J.; DE BRITTO, LUIZ R. G.; et al. [C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 35, p. 108-115, OCT 2019. (13/25049-2)