Aluminium affects neurospheres at human in vivo relevant concentrations
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Aluminium affects neurospheres at human in vivo relevant concentrations Christoph van Thriel1 Received: 17 August 2020 / Accepted: 18 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Recently, Karine Reichert and colleagues from the Federal University of Santa Maria in Brazil published a study about the effects of aluminium on neural progenitor cells (Reichert et al. 2019). The authors established an in vitro test with neurospheres isolated from embryonic telencephalons (Hutton and Pevny 2008). With this system, they evaluated toxicity of Al3+ in the chloride form (AlCl3). They report that Al3+ at 100 µM caused cytotoxicity as evidenced by decreased diameters of the neurospheres (Reichert et al. 2019). At 10 µM, mitochondrial potential was reduced and a first increase in the percentage of apoptotic cells was already seen at 1 µM Al3+. Aluminium occurs ubiquitously in the environment, exposure occurs via food and drinking water and Al3+ can pass the blood–brain barrier and accumulate in the brain (Exley 2013; Saiyed and Yokel 2005; Becaria et al. 2002). Therefore, it is interesting to compare the concentration ranges observed in humans in vivo to the concentrations that caused toxicity in vitro in the neurosphere assay of Reichert and colleagues. Aluminium concentrations in the blood of non-occupationally exposed individuals were reported to be approximately 0.1 µM; electrophoresis workers showed concentrations between 0.74 and 1.1 µM before shift, which increased during the shift by up to 2.2 µM (Schlatter et al. 1986, 1990). Blood levels of 7 µM or more are usually associated with clinical symptoms and toxicity. Therefore, the current study of Reichert (2019) is of relevance, because it shows in vitro toxicity at in vivo relevant concentration ranges. In recent years, much effort has been invested to establish tests for analysis of neurotoxicity or developmental neurotoxicity (Frimat et al. 2010; Noorafshan and Rafati 2017; * Christoph van Thriel [email protected] 1
Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139 Dortmund, Germany
Krug et al. 2013; Zimmer et al. 2014; Kandhare et al. 2017; Leist et al. 2017; Sachinidis et al. 2019). Key findings are that three concentration ranges can be differentiated: a high range where cytotoxicity and gene expression changes occur, intermediate concentrations with gene expression changes without cytotoxicity and concentration ranges of tolerance, where neither cytotoxicity and concentration ranges of tolerance, where neither cytotoxicity nor expression changes are induced (Waldmann et al. 2014, 2017; Shinde et al. 2016, 2017; Balmer et al. 2014). The patterns of altered gene expression allowed the identification of the type of neurotoxic agents, e.g. the differentiation of histone deacetylase inhibitors and mercurials (Rempel et al. 2015; Pallocca et al. 2016). Despite of numerous studies with gold standard compounds, e.g. aluminium in the case of Reichert et al. (201
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