Aluminum affects neural phenotype determination of embryonic neural progenitor cells

Author(s)

Reichert, Karine P. ^[1] ; Schetinger, Maria Rosa C. ^[1] ; Pillat, Micheli M. ^{[2, 1]} ; Bottari, Nathieli B. ^[1] ; Palma, Tais V. ^[1] ; Gutierres, Jessie M. ^[3] ; Ulrich, Henning ^[2] ; Andrade, Cinthia M. ^[1] ; Exley, Christopher ^[4] ; Morsch, Vera M. M. ^[1]

Affiliation

^[1] Fed Univ Santa Maria UFSM, Dept Biochem & Mol Biol, Postgrad Program Toxicol Biochem, Lab Toxicol Enzymol, BR-97105900 Santa Maria, RS - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

^[3] Fed Univ Hlth Sci Porto Alegre UFCSPA, Lab Res Pathol, Porto Alegre, RS - Brazil

^[4] Keele Univ, Birchall Ctr, Lennard Jones Labs, Keele ST5 5BG, Staffs - England

• Document type: Journal article
• Source: ARCHIVES OF TOXICOLOGY; v. 93, n. 9, p. 2515-2524, SEP 2019.
• Web of Science Citations: 1

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 mu M) 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 mu M 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 mu M Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker beta 3-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. (AU)

• FAPESP's process: 15/19478-3 - Role of kinin-B2 receptor in pathogenesis and progression of familial Alzheimer's Disease: from neurogenesis and immune response to cognition
• Grantee: Micheli Mainardi Pillat
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support type: Research Projects - Thematic Grants