Characterization of the effects of phosphodiestrerase 10A inhibition on c-fos expression in the striatum of dyskinetic rats

• Grant number: 19/26152-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fernando Eduardo Padovan Neto
• Grantee: Mirella Rosine Corrêa
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/00003-0 - Role of neuronal nitric oxide synthase and phosphodiesterase 10A in striatal medium spiny neuron activity during L-Dopa-induced dyskinesia, AP.JP

Abstract

Among the main pathological evidence affecting Parkinson's disease (PD) patients is the death of dopaminergic neurons of the substantia nigra pars compacta. Dopamine replacement can be done with L-3,4-dihydroxyphenylalanine (L-DOPA) but chronic use of this drug is associated with the onset of motor complications known as L-DOPA-induced dyskinesias (LIDs). Inhibition of the phosphodiesterase 10A (PDE10A) enzyme is a promising therapy for LIDs because of its ability to modulate the signaling pathways involved in inappropriate motor response. This enzyme is abundantly located within the striatum, which is a structure of the basal ganglia involved in the elaboration of the appropriate motor response. In this study, we will evaluate the antidyskinetic potential of a PDE10A enzyme inhibitor in a preclinical model of PD and investigate how PDE10A inhibition correlates with c-Fos expression in striatal projection neurons. (AU)