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PATHOPHYSIOLOGICAL MECHANISMS AND NEUROPROTECTIVE INTERVENTIONS IN A PROGRESSIVE ANIMAL MODEL OF PARKINSON'S DISEASE

Grant number: 15/03354-3
Support type:Regular Research Grants
Duration: November 01, 2015 - April 30, 2018
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Regina Helena da Silva
Grantee:Regina Helena da Silva
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Alessandra Mussi Ribeiro

Abstract

Parkinson´s disease is the second most prevalent age-related neurodegenerative disorder. The main symptoms of this pathology are severe motor deficits, but non-motor signs are also present. The pathophysiology comprises a progressive neuronal loss, and there is currently no effective intervention for slowing the degeneration. There is evidence of an important role of neuronal oxidative stress, inflammation processes and ±-synuclein accumulation in the mechanisms leading to degeneration, which affects mostly dopaminergic neurons. This highlights the importance of the investigation of neuroprotective strategies. Currently used animal models of PD present limitations regarding the investigation of possible neuroprotective treatments. In general, the models involve neurotoxins that leads to immediate severe motor impairment, precluding the evaluation of possible delays in the symptoms progression. We have recently validated a protocol for the study of PD symptoms progression: the repeated treatment with a low dose of reserpine (RES, a vesicular monoamine transporter inhibitor). At high doses, RES induces immediate motor damage. The repeated administration of a ten times lower dose produces progressive motor deficits and non-motor symptoms, together with oxidative damage and reduction in tyrosine hydroxylase. Although this protocol has great potential for the study of PD, it is necessary to better characterize some pathophysiological aspects compatible to the human condition. Our goals are: 1- to extend the validation of the progressive RES model of PD by the investigation of inflammation, neuronal death and ±-synuclein levels parameters and 2- to investigate the effects of classical antioxidants and a natural product with antioxidant potential on the development of the behavioral and neuronal alterations in rats subjected to the progressive RES model of DP. The results will be compared to the effects of these neuroprotective attempts in conventional acute models. (AU)

Scientific publications (7)
(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)
BESERRA-FILHO, JOSE I. A.; DE MACEDO, AMANDA M.; LEAO, ANDERSON H. F. F.; BISPO, JOSE MARCOS M.; SANTOS, JOSE R.; DE OLIVEIRA-MELO, ALLAN JOHN; MENEZES, PAULA DOS PASSOS; DUARTE, MARCELO C.; DE SOUZA ARAUJO, ADRIANO A.; SILVA, REGINA H.; QUINTANS-JUNIOR, LUCINDO J.; RIBEIRO, ALESSANDRA M. Eplingiella fruticosa leaf essential oil complexed with beta-cyclodextrin produces a superior neuroprotective and behavioral profile in a mice model of Parkinson's disease. Food and Chemical Toxicology, v. 124, p. 17-29, FEB 2019. Web of Science Citations: 1.
MEDEIROS, ANDRE DE MACEDO; SILVA, REGINA HELENA. Sex Differences in Alzheimer's Disease: Where Do We Stand?. JOURNAL OF ALZHEIMER'S DISEASE, v. 67, n. 1, p. 35-60, 2019. Web of Science Citations: 0.
LINS, LIVIA CRISTINA R. F.; SOUZA, MARINA F.; BISPO, JOSE MARCOS M.; GOIS, AUDERLAN M.; MELO, THAIS CRISTINA S.; ANDRADE, RAYR ANTONIO S.; QUINTANS-JUNIOR, LUCINDO J.; RIBEIRO, ALESSANDRA M.; SILVA, REGINA H.; SANTOS, JOSE R.; MARCHIORO, MURILO. Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine. Brain Research Bulletin, v. 139, p. 9-15, MAY 2018. Web of Science Citations: 6.
CAMPELO, CLARISSA L. C.; SANTOS, JOSE R.; SILVA, ANATILDES F.; DIERSCHNABEL, MINE L.; PONTES, ANDRE; CAVALCANTE, JEFERSON S.; RIBEIRO, ALESSANDRA M.; SILVA, REGINA H. Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice. Behavioural Brain Research, v. 328, p. 138-148, JUN 15 2017. Web of Science Citations: 9.
LEAO, ANDERSON H. F. F.; MEURER, YWLLIANE S. R.; DA SILVA, ANATILDES F.; MEDEIROS, ANDRE M.; CAMPELO, CLARISSA L. C.; ABILIO, VANESSA C.; ENGELBERTH, ROVENA C. G. K.; CAVALCANTE, JEFERSON S.; IZIDIO, GEISON S.; RIBEIRO, ALESSANDRA M.; SILVA, REGINA H. Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expression. FRONTIERS IN AGING NEUROSCIENCE, v. 9, MAR 27 2017. Web of Science Citations: 4.
MATEUS BRANDAO, LUIZ EDUARDO; MORAIS FERREIRA NOGA, DIANA ALINE; DIERSCHNABEL, ALINE LIMA; DAS CHAGAS CAMPELO, CLARISSA LOUREIRO; RODRIGUES MEURER, YWLLIANE DA SILVA; LIMA, RAMON HYPOLITO; GALVAO JANUARIO ENGELBERTH, ROVENA CLARA; CAVALCANTE, JEFERSON SOUZA; LIMA, CLESIO ANDRADE; MARCHIORO, MURILO; ESTEVAM, CHARLES DOS SANTOS; SANTOS, JOSE RONALDO; SILVA, REGINA HELENA; RIBEIRO, ALESSANDRA MUSSI. Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease. Evidence-based Complementary and Alternative Medicine, 2017. Web of Science Citations: 3.
PERES, FERNANDA F.; LEYIN, RAQUEL; SUIAMA, MAYRA A.; DIANA, MARIANA C.; GOUVEA, DOUGLAS A.; ALMEIDA, VALERIA; SANTOS, CAMILA M.; LUNGATO, LISANDRO; ZUARDI, ANTONIO W.; HALLAK, JAIME E. C.; CRIPPA, JOSE A.; D'ALMEIDA, VANIA; SILVA, REGINA H.; ABILIO, VANESSA C. Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats. FRONTIERS IN PHARMACOLOGY, v. 7, SEP 28 2016. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.