Modelo experimental de fase pré-clínica de doença de Parkinson por infusão intranasal com 1-metil-4-fenil-1,2,3,6-tetrahidropiridina em camundongo: análise estrutural e funcional do mesencéfalo ventral e núcleo estriado

Abstract

Parkinson's disease (PD) is a progressive and irreversible neurodegenerative disease whose main histopathologic characteristic is the death of dopaminergic neurons in the compact part of the substantia nigra (SNpc, substantia nigra pars compacta) in the midbrain. The classic symptoms of PD taken as cardinal and decisive for diagnosis are: bradykinesia, rigidity, resting tremor and postural instability. It is the second most common neurodegenerative disease in humans and, according to the data of the Associação Brasileira de Parkinson (Brazilian Parkinsons Association), there are over 200,000 affected Brazilians. The etiology of PD has not been fully understood yet and may involve various factors such as genetic factors, senescence, oxidative stress, mitochondrial dysfunction, neuroinflammation and exposure to environmental toxins. In this work, we evaluate the locomotor activity, the levels of neurotrophic factors and cytokines as well as the ultrastructural alterations in the ventral midbrain and the striatum of C57BL/6 mice after intranasal infusion of MPTP. Our results showed that at the 11th day post-infusion of MPTP (1mg/nostril) it was not possible to observe any alteration in locomotor ability of those animals. However, the mice exhibited a pattern of anxious behavior in open field test. At the same period post infusion, it was possible to detect increased levels of IL-10 and IL-17 in the ventral midbrain, and IL-17 in the striatum. Concerning neurotrophic factors, we have observed decreased levels of BDNF in the ventral midbrain, and increased BDNF and NGF levels in the striatum. Ultrastructural analyses of the ventral midbrain and striatum have not revealed any significant morphologic alteration. Preliminary results with KO p55 TNF at day 11th post infusion of MPTP showed degenerative changes in the neurons of ventral midbrain and striatum. Our results indicate that the experimental model might be associated to the preclincl phase of PD and open new perspectives for studying the factors that might interfere with the progression of this disease. Therefore, this model mimics pre-clinical symptoms of PD