Analysis of nitric oxide synthase in dopaminergic and non dopaminergic neurons in experimental Parkinson Disease: role of NOS inhibitors in L-DOPA induced diskinesias

Principal Investigator:

Elaine Aparecida Del Bel Belluz Guimarães

Awardee:

Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto, SP, Brazil
Principal investigator abroad: Rita Raisman-Vozari
Institution abroad: Institut National de la Santé et de la Recherche Médicale (Inserm). (France)
Field of knowledge:Biological Sciences - Physiology
Support type:Regular Research Awards
Grant number: 08/55092-9
Duration: January 01, 2009 - March 31, 2013
Cooperation agreement with FAPESP: INSERM
Abstract
There is evidence that nitric oxide plays a role in the neurotransmitter balance within the basal ganglia and in the pathology of Parkinson's disease (PD). Treatment with the L-NOARG reduced 6-OHDA-induced dopaminergic damage in the dorsal striatum, ventral substantia nigra and lateral globus pallidus. L-NOARG reduced 6-OHDA-induced striatal increase, and substantia nigra compacta decrease, in the density of neuronal nitric oxide synthase (nNOs) positive cells. L-DOPA treatment of PD induces severe motor fluctuations and the development of abnomial involuntary movements, referred to as l-DOPA-induced dyskinesia. It is conceivable that nitrergic mechanisms also contribute to the pathogenesis of l-DOPA response changes. Since it is likely that NOS inhibitors may influence motor behavior, pharmacological blockade of NOS could improve therapeutic efficacy in certain clinical situations. The specific aims of this project are to analyze the role of Nitric Oxide system on neuroprotective/neuroplastic processes in experimental PD and dykinesia induced in rats. In this project we will answer to the following questions: 1- Which are the anatomical relationship of dopaminergic and non-dopaminergic system with nitrergic system in different brain regions regulating motor functions in PD? 2-Which are the consequences of a chronic treatment with a NOS inhibitors on L-DOPA induced diskinesias in an animal model of PD? 3- Which is the role of NOS donators, inhibitors, in the release of DA in mesencephalic cultures? (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)
PREDIGER, RUI D. S.; AGUIAR, JR., ADERBAL S.; ROJAS-MAYORQUIN, ARGELIA ESPERANZA; FIGUEIREDO, CLAUDIA P.; MATHEUS, FILIPE C.; GINESTET, LAURE; CHEVARIN, CAROLINE; DEL BEL, ELAINE; MONGEAU, RAYMOND; HAMON, MICHEL; LANFUMEY, LAURENCE; RAISMAN-VOZARI, RITA. Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson's Disease. NEUROTOXICITY RESEARCH, v. 17, n. 2, p. 114-129, FEB 2010.
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