Vitamin D3 actions on astrocyte cells: A target for therapeutic strategy in Parkinson's disease?

Autor: de Siqueira EA; The Federal University of Ceará, Fortaleza, Brazil., Magalhães EP; The Federal University of Ceará, Fortaleza, Brazil., de Menezes RRPPB; The Federal University of Ceará, Fortaleza, Brazil., Sampaio TL; The Federal University of Ceará, Fortaleza, Brazil., Lima DB; The Federal University of Ceará, Fortaleza, Brazil., da Silva Martins C; The Federal University of Ceará, Fortaleza, Brazil., Neves KRT; The Federal University of Ceará, Fortaleza, Brazil., de Castro Brito GA; The Federal University of Ceará, Fortaleza, Brazil., Martins AMC; The Federal University of Ceará, Fortaleza, Brazil., de Barros Viana GS; The Federal University of Ceará, Fortaleza, Brazil. Electronic address: gbviana@live.com.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2023 Jan 10; Vol. 793, pp. 136997. Date of Electronic Publication: 2022 Dec 02.
DOI: 10.1016/j.neulet.2022.136997
Abstrakt: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic cells in the substantia nigra pars compacta. PD patients' brains show neuroinflammation, oxidative stress, and mitochondrial dysfunction. The present study aims to evaluate the neuroprotective activity of VD3 on astrocytes after their exposure to rotenone (ROT) a natural pesticide known to exhibit neurotoxic potential via the inhibition of mitochondrial complex I. Cell viability parameters were evaluated by the MTT test and staining with 7-AAD in cultures of astrocytes treated and untreated with VD3 (0.1, 0.5, and 1.0 ng/mL) and/or ROT (10 µg/mL or 5 µg/mL), and the cytoplasmic production of ROS and the cell death profile were measured by flow cytometry. Glutathione accumulation and ultrastructural changes were evaluated and immunocytochemistry assays for NF-kB and Nrf2 were also carried out. The results showed that VD3 improved the viability of cells previously treated with VD3 and then exposed to ROT, reducing the occurrence of necrotic and apoptotic events. Furthermore, cells exposed to ROT showed increased production of ROS, which decreased significantly with previous treatment with VD3. Importantly, the decrease by ROT in the mitochondrial transmembrane potential was significantly prevented after treating cells with VD3, especially at a concentration of 1 ng/mL. Therefore, treatment with VD3 protected astrocytes from damage caused by ROT, decreasing oxidative stress, decreasing NF-kB and Nrf2 expressions, and improving mitochondrial function. However, further investigation is needed regarding the participation and mechanism of action of VD3 in this cellular model of PD focusing on the crosstalk between Nrf2 and NF-kB.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: