Estudo de sintomas não-motores em modelo experimental de doença de parkinson por infusão intranasal de MPTP: uma análise comportamental e imunológica

Abstract

Parkinson's disease (PD) is known for its motor symptoms: resting tremor, bradykinesia, rigidity, postural instability and festination. Although motor symptoms are better known, there is evidence of non-motor symptoms that may precede the appearance of motor alterations by years. Among these non-motor symptoms are behavioral and cognitive changes such as: hyposmia, depression and anxiety, cognitive decline, sleep disorders and constipation. Although the mechanisms involved in PD remain poorly elucidated, the death of dopaminergic neurons in Substantia Nigra pars Compacta (SNpc) and the consequent alteration of the nigrostriatal pathway seem to play an important role in the pathophysiology of the disease. Several factors have been implicated in dopaminergic degeneration such as genetics, senescence, oxidative stress, mitochondrial dysfunction, neuroinflammation and exposure to environmental toxins. Many studies describe microglia changing its morphology and secreting pro-inflammatory cytokines, neurotoxins and reactive oxygen species (ROS) in response to some inflammatory trigger. The animal model by intranasal infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mimics aspects of the early stage of the disease, however the role of the immune system in the pathophysiology of these non-motor symptoms has been little explored. In the present study, animals that received intranasal infusion of MPTP showed significant impairment of olfactory and social memory as well as compulsive and anxious-type behavior. Non-motor symptoms are associated with glial activation and changes in inflammatory mediators and neurotrophic factors in the substantia nigra and striatum. Thus, the MPTP intranasal infusion model is able to mimic early clinical aspects of PD as well as inflammatory processes involved in the pathophysiology of the disease. This model can be a valuable tool for the study of cellular and molecular mechanisms involved in PD as well as for the identification and development of therapeutic strategies focused on minimizing or preventing PD-associated non-motor and motor symptoms.