Aluminum-induced alterations of purinergic signalling in embryonic neural progenitor cells

Author(s):Show less -

Reichert, Karine P. ^[1] ; Pillat, Micheli M. ^[2] ; Schetinger, Maria Rosa C. ^[1] ; Bottari, Nathieli B. ^[1] ; Palma, V, Tais ; Assmann, Charles E. ^[3] ; Gutierres, Jessie M. ^[4] ; Ulrich, Henning ^[2] ; Andrade, Cinthia M. ^[3] ; Exley, Christopher ^[5] ; Morsch, Vera M. M. ^[3]

Affiliation

^[1] Fed Univ Santa Maria UFSM, Dept Biochem & Mol Biol, CCNE, Postgrad Program Biol Sci Toxicol Biochem, Santa Maria, RS - Brazil

^[2] Fed Univ Santa Maria RS, Hlth Sci Ctr, Dept Microbiol & Parasitol, Santa Maria, RS - Brazil

^[3] Palma, Tais, V, Fed Univ Santa Maria UFSM, Dept Biochem & Mol Biol, CCNE, Postgrad Program Biol Sci Toxicol Biochem, Santa Maria, RS - Brazil

^[4] Fed Univ Hlth Sci Porto Alegre UFCSPA, Lab Res Pathol, Porto Alegre, RS - Brazil

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

• Document type: Journal article
• Source: Chemosphere; v. 251, JUL 2020.
• Web of Science Citations: 0

Abstract

The ubiquitous presence of aluminum in the environment leads to a high likelihood of human exposure. Neurotoxicity of the trivalent cationic form of this metal (Ak3+) occurs in the central nervous system via accumulation of Al in cells of neural origin, including neural progenitor cells (NPCs). NPCs play a key role in the development and regeneration of the brain throughout life; therefore, this metal may contribute to neuropathological conditions. Here, we evaluated the effects of different Al3+ concentrations (0-50 mu M) on the purinergic system of NPCs isolated from embryonic telencephalons, cultured as neurospheres. Al3+ adhered to the cell surface of neurospheres reducing extracellular ATP release, as well as ATP, ADP, and AMP hydrolysis by NTPDase and 5'-nucleotidase, respectively. In addition, impaired nucleotide release by Al3+ reduced P2Y1 and adenosine A2A receptors expression in differentiated neurospheres. These receptors are crucial for NPC proliferation during brain development and self-repair against external stimuli, such as metal exposure. Thus, Al3+ represents an environmental agent linked to neurodegeneration through alterations in the ATP-signalling pathway, proving to be a potential mechanism associated with NPC proliferation and brain degeneration. (C) 2020 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral