Browsing by Author "Fiadeiro, Mariana Bernardo"
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- Modulatory effect of innovative antioxidant formulation on Parkinson’s disease neurodegeneration and neurogenesisPublication . Fiadeiro, Mariana Bernardo; Cristovão, Ana Clara Braz; Bernardino, Liliana InácioParkinson’s disease (PD) is a multifactorial neurological disorder characterized by increased levels of oxidative stress. Neurogenesis, a process of generating functional neurons, is also affected in PD. Inline, antioxidant compounds may be used to prevent neurodegeneration and modulate neurogenesis. Several antioxidant compounds exhibit low solubility requiring the use of vehicles that, in turn, may be neurotoxic. Therefore, the development of new delivery formulations capable to overcome these problems and simultaneously prompt the concentration of antioxidant compounds in the brain is urgent. Herein, the cytotoxicity of [Chol][Apo] was tested in N27 neuronal cell line and Subventricular Zone (SVZ) neural stem cells (NSCs) primary cultures, and its capability to prevent dopaminergic neurodegeneration in experimental models of PD and modulate neurogenesis process. The results showed that [Chol][Apo] induced a low toxic effect on dopaminergic neurons and additionally, it was capable to significantly reduce in vitro neuronal death induced by 6-OHDA. Moreover, the results reveal that the range of [Chol][Apo] concentrations used did not induce necrosis/late-apoptosis to NSCs from the SVZ. NSCs and neuroblasts proliferation was not affected compared with control and the same was verified for neuronal differentiation. In vivo, the infusion of 15 µg/µL/h of [Chol][Apo] in the ventricle during 7 days significantly reduced the neurotoxic effect of 6-OHDA on DA neurons in the SN. Furthermore, there is a tendency that suggests that the new antioxidant formulation may increase neuroblast population in healthy and in 6-OHDA-treated mice. On the contrary, [Chol][Apo] did not alter the number of proliferating neuroblasts in the SVZ of healthy and 6-OHDA-treated mice. The results showed an increase of proliferating mature neurons in the ST of 6-OHDA-treated mice. Altogether, these results opened the possibility to further investigate the role of [Chol][Apo] on PD neurodegeneration and on neurogenesis and its development as a new therapeutic approach to halt PD progression.