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Arch Toxicol. 2019 Jul 30. doi: 10.1007/s00204-019-02522-6. [Epub ahead of print]

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Author information

1
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. kakareichert@yahoo.com.br.
2
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.
3
Department of Biochemistry, Institute of Chemistry, University of São Paulo (USP), São Paulo, SP, Brazil.
4
Laboratory of Research in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
5
Lennard-Jones Laboratories, Birchall Centre, Keele University, Staffordshire, ST5 5BG, UK.
6
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. veramorsch@gmail.com.

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.

KEYWORDS:

Aluminum; Aluminum-free ion (Al3+); Neural phenotype; Neurodegenerative disorder; Neurogenesis; Neurospheres

PMID:
31363819
DOI:
10.1007/s00204-019-02522-6

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