Abstract
Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer’s disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form—AlCl3) at different concentrations (0.1–100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker β3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.
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Acknowledgements
This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Process Number: 306238/2017-9), Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS/PRONEX—Process Number: 16/2551-0000499-4) and Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/—Process Number: 88882.182146/2018-01). HU acknowledges grant support by Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation FAPESP Project No. 2012/50880-4). MMP is grateful for a post doctoral fellowship from FAPESP (Project No. 2015/19478-3).
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Reichert, K.P., Schetinger, M.R.C., Pillat, M.M. et al. Aluminum affects neural phenotype determination of embryonic neural progenitor cells. Arch Toxicol 93, 2515–2524 (2019). https://doi.org/10.1007/s00204-019-02522-6
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DOI: https://doi.org/10.1007/s00204-019-02522-6