Aluminum affects neural phenotype determination of embryonic neural progenitor cells

Autor: Jessié Martins Gutierres, Karine Paula Reichert, Henning Ulrich, Cinthia Melazzo de Andrade, Maria Rosa Chitolina Schetinger, Micheli M. Pillat, Nathieli B. Bottari, Vera Maria Morsch, Christopher Exley, Taís Vidal Palma
Rok vydání: 2019
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1432-0738
0340-5761
DOI: 10.1007/s00204-019-02522-6
Popis: 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.
Databáze: OpenAIRE
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