Estudo de marcadores imunofarmacológicos e suas associações com sintomas não-motores na doença de Parkinson

Abstract

Although Parkinsons disease (PD) is considered a motor disturbance, non-motor symptoms (NMS) associated with PD are considered as disabling as the motor signs. Inflammatory mechanisms have been implicated in a series of NMS including behavioral disturbances, cognitive dysfunction and mood disorders, especially depressive symptoms. Accumulating evidence strongly suggest the involvement of inflammation in PD pathophysiology. Therefore, this study aimed to assess NMS in PD, mainly depressive symptoms and cognitive deficit and evaluate the association of these clinical variables with immune/inflammatory changes in the peripheral blood. For that reason, we enrolled 48 PD patients and 29 controls, who were subject to the clinical evaluation and peripheral blood drawn. We analyzed plasma levels of cytokines, chemokines, neurotrophic factors and we performed immunophenotyping and assessment of dopaminergic and serotonergic receptors in the leukocytes. PD patients presented poorer performance on the cognitive tests and higher scores on the depressive symptoms scale in comparison with controls. In addition, the severity of depressive symptoms was associated with disease severity, as evaluated by the motor scale. Regarding the plasma molecules, PD patients presented higher levels of soluble tumor necrosis factor receptors (sTNFRs) than control individuals. Among PD patients, higher sTNFRs and IP-10 levels were associated with poorer cognitive tests scores. Regarding immunophenotyping data, PD patients presented decreased percentage of T lymphocytes (CD3+), specifically lower percentage of T activated lymphocytes (CD4+CD25+) when compared to controls. Corroborating these results, PD patients presented reduced plasma levels of the inflammatory cytokines IL-4, IL-6, IL-10, TNF, IFN- and IL-17A. In vitro experiments using cells from healthy and young donors demonstrated that the production of cytokines by peripheral blood mononuclear cells was reduced after exposure to the antiparkinsonian drugs levodopa and pramipexole. In addition, the percentages of expression of dopaminergic and serotonergic receptors are altered in the peripheral blood of PD patients. It is not clear if the differences that we have found are due to adaptive mechanisms to the changes that occur in PD, including pharmacological treatment, or if they are directly related to the disease pathophysiology. More studies are needed in this regard.