Vulnerability of selected strains for innate or adaptative immune response to parkinsonian lesion inductors

• Grant number: 15/20789-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Lanfranco Ranieri Paolo Troncone
• Grantee: Michele Marinho Soares
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Laboratory, epidemiological and therapeutic studies in humans and animals, suggest that neuroinflammatory processes are involved in Parkinson's disease. The intervention on inflammation has been the object of study to prevent or delay the progression of this disease. Strains of animals capable to produce strong or weak inflammatory responses can be used to challenge the involvement of inflammatory processes in several pathologies. We investigated the susceptibility of two inbred strains of mice selected for their ability to produce high (AIRmax) or low (AIRmin) acute inflammatory to neurotoxins 1-Methyl-4-phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and rotenone . Groups of young males (3 months) and adults (6 months) having BALB/c and C57BL/6 as control, were used in animal models of Parkinson's disease induced by treatment with MPTP (4 x 20 mg/kg or 5 x 20mg/kg s.c. every 2 hours in a single day) and rotenone (chronic treatment: continuous s.c. infusion of 3, 6 and 12 mg/kg/day by Alzet osmotic pump for 28 days or sub-chronic treatment: i.p. injection at a dose of 3 mg/kg/day for 10 days). The animals were evaluated by rotarod apparatus in sessions of 5 minutes and constantly increasing speed from 5 to 50 rpm, measuring the time spent on the rotating bar. Results of behavioral testing failed to clearly establish differences between the lineages and controls regarding susceptibility to the Parkinsonian neurotoxins. Although, it is known that motor symptoms arise only after extensive lesions of the dopaminergic systems, therefore this question is still open. In this study we intend to evaluate the extension of the neurotoxin-induced dopaminergic lesion by immune-histochemistry against tyrosine-hydroxylase and CD11b, a microglial activation marker used to evaluate neuro-inflammation. (AU)