Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Arch Toxicol 2019 Sep 30;93(9):2515-2524. Epub 2019 Jul 30.

Post-Graduate Program in Toxicological Biochemistry, Laboratory of Toxicological Enzymology, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al) 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 Al (in the chloride form-AlCl) 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 Al at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al 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 Al caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

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http://dx.doi.org/10.1007/s00204-019-02522-6DOI Listing
September 2019
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