DOI: 10.1007/s12640-016-9678-5 Pages: 245-258
Article Type: ORIGINAL ARTICLE

Cytotoxic Effects of Environmental Toxins on Human Glial Cells

1. The University of New South Wales, School of Biotechnology and Biomolecular Sciences

2. The University of New South Wales, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine

3. Macquarie University, Faculty of Medicine and Health Science, Neuroinflammation group

4. Université de Toulouse, UPS, UMR-152 (Pharma-Dev)

5. Institut de Recherche pour le Développement (IRD), UMR-152

6. Pacific Biotech SAS

7. Université de la Polynésie française, Ecosystèmes Insulaires Océaniens, UMR-241

8. Ecosystèmes Insulaires Océaniens UMR-241, Institut Louis Malardé, Laboratoire de recherche sur les Microalgues Toxiques

9. Prince of Wales Hospital, Minimally Invasive Cancer Centre

Correspondence to:
Brett A. Neilan
Tel: +61-2-9385 3235
Email: b.neilan@unsw.edu.au

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Abstract

Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.

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  • Accepted: Oct 14, 2016
  • Online: Oct 29, 2016
  • Revised: Sep 29, 2016

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