RISK FACTOS FOR PARNINSON'S DISEASE IN A RESERPINE-INDUCED PROGRESSIVE ANIMAL MODEL

• Grant number: 17/26253-3
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2018
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Regina Helena da Silva
• Grantee: Regina Helena da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• City of the host institution: São Paulo

Abstract

Parkinson's disease (DP) is the second most prevalent age-related neurodegenerative disorder. PD comprises motor and non-motor symptoms and it's pathophysiology is related to progressive neuronal loss in the substantia nigra pars compacta. There is no known intervention that delays this progression, and at the onset of the motor symptoms, approximately 70% of the neurons have already been lost. This renders possible neuroprotective interventions very difficult to accomplish. Thus, the investigation of factors that suggest preventive interventions in the absence of symptoms is very relevant. While there are still no biological markers for a pre-symptomatic diagnosis, several risk factors have been identified in the clinical literature. However, because PD is pharmacologically or genetically induced in animal models, there is a lack of studies on increasing or decreasing risk factors in such models. One of the limitations for the investigation of risk factors in animal models is the induction of severe immediate motor deficits that precludes the evaluation of differences between groups of animals with or without a certain risk factor. Recently, we proposed the repeated treatment with a low dose of reserpine (a monoamine vesicular transporter blocker) for the study of PD progression. This protocol induces progressive motor and non-motor signs, accompanied by brain oxidative damage, decrease in dopamine markers and increase in alpha-synuclein expression (a neuropathological hallmark of PD). In this project, we will investigate if well characterized increasing or decreasing risk factors for PD influence the development of motor and non-motor symptoms in the progressive parkinsonism model induced by reserpine. The following risk factors will be investigated: aging, male sex, stress, depression and sleep disturbances (increasing risk factors); and caffeine and nicotine consumption (decreasing risk factors). Additionally, we will investigate possible neuronal and physiological factors related to the mentioned risk factors (dopaminergic markers, oxidative stress parameters, alpha-synuclein levels and hormonal factors). (AU)

Scientific publications

(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)

SILVA, PHIETICA R. R.; SILVA, REGINA H.; LIMA, RAMON HYPOLITO; MEURER, YWLLIANE S.; CEPPI, BRUNO; YAMAMOTO, MARIA EMILIA. Are There Multiple Motivators for Helping Behavior in Rats?. FRONTIERS IN PSYCHOLOGY, v. 11, JUL 29 2020. (17/26253-3)

BECEGATO, MARCELA; MEURER, YWLLIANE S. R.; PAIVA-SANTOS, MURILO A.; LIMA, ALVARO C.; MARINHO, GABRIELA F.; BIONI, VINICIUS S.; SOARES, MANUELA B. L.; LEAO, ANDERSON H. F. F.; SUCHECKI, DEBORAH; SILVA, REGINA H.. Impaired discriminative avoidance and increased plasma corticosterone levels induced by vaginal lavage procedure in rats. Physiology & Behavior, v. 232, APR 1 2021. (17/26253-3)

LOPES-SILVA, L. B.; CUNHA, D. M. G.; LIMA, A. C.; BIONI, V. S.; GONCALVES, N.; KURITA, J. P. F.; WUO-SILVA, R.; SILVA, R. H.. Sleep deprivation induces late deleterious effects in a pharmacological model of Parkinsonism. Experimental Brain Research, v. 242, n. 5, p. 16-pg., 2024-03-18. (17/26253-3, 15/03354-3)