Efeito do flavonoide rutina em marcadores neurais da zona subventricular, hipocampo e estriado em modelo in vivo da doença de Parkinson

Abstract

Aminochrome, a dopamine-derived neurotoxin, is used to induce degeneration in animal models of Parkinson’s disease. In addition to dopaminergic neuronal loss, this condition also involves glial reactivity and reduced neurogenesis. M1-type microglia and A1 type astrocytes contribute to a toxic and pro-inflammatory environment. Therefore, investigating agents with regulatory effects on glial cells represents a promising approach for the development of neuroprotective therapies. This study investigates the effects of rutin on adult neurogenesis and glial activation in an aminochrome-induced model of Parkinson’s disease. Methods: Twenty-four male Wistar rats (250–270 g) were randomly assigned to four groups. The CT and RUT groups received saline solution, while the AMI and AMI+RUT groups received aminochrome (1,000 µM; 6 nmol in 6 µL) via striatal injection. Following 22 days of oral treatment with rutin or vehicle by gavage, the brains were processed for immunofluorescence using markers for astrocytes (GFAP, S100β), microglia (IBA1, CD68, CD206), and neurons (DCX, NeuN). Results and Conclusions: The study found that aminochrome induced alterations in the striatum, affecting microglia and astrocytes, as indicated by an increased number of microglial cells (IBA1 and CD68) and elevated levels of GFAP and S100β. These changes were attenuated by rutin administration. Although striatal toxin injection may have indirectly triggered other mechanisms in the hippocampus, no aminochrome-induced glial reactivity or reduction in neurogenesis was observed in this region. The main contribution of this work was to show that oral administration of rutin modulated the expression of glial markers in the striatum and hippocampus of Wistar rats, increasing M1 associated markers, reducing those linked to the M2 profile, and decreasing neuronal precursor markers in the hippocampus, while simultaneously increasing their expression in the subventricular zone. These findings underscore a potential relationship between the neuroprotective effect of rutin and the dynamics of glial activation, contributing to a better understanding of its mechanisms of action in the context of Parkinson’s disease.