title: Cytotoxic Effects of Environmental Toxins on Human Glial Cells.
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.
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Fiona
authors: F
authors: D'Mello
authors: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, The University of New South Wales, Sydney, Australia.
authors: Nady
authors: N
authors: Braidy
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Helder
authors: H
authors: Marçal
authors: Faculty of Medicine and Health Science, Neuroinflammation group, Macquarie University, Sydney, Australia.
authors: Gilles
authors: G
authors: Guillemin
authors: Université de Toulouse, UPS, UMR-152 (Pharma-Dev), rte de Narbonne, cedex 9, F-31062, Toulouse, France.|Institut de Recherche pour le Développement (IRD), UMR-152, BP 529, 98713, Tahiti, Papeete, French Polynesia.|Pacific Biotech SAS, BP 140 289, 98701, Tahiti, Arue, French Polynesia.|Ecosystèmes Insulaires Océaniens, UMR-241, Université de la Polynésie française, BP 6570, 98702, Tahiti, Faa'a, French Polynesia.
authors: Fanny
authors: F
authors: Rossi
authors: Ecosystèmes Insulaires Océaniens UMR-241, Institut Louis Malardé, Laboratoire de recherche sur les Microalgues Toxiques, BP 30, 98713, Tahiti, Papeete, French Polynesia.
authors: Mirielle
authors: M
authors: Chinian
authors: Université de Toulouse, UPS, UMR-152 (Pharma-Dev), rte de Narbonne, cedex 9, F-31062, Toulouse, France.|Institut de Recherche pour le Développement (IRD), UMR-152, BP 529, 98713, Tahiti, Papeete, French Polynesia.
authors: Dominique
authors: D
authors: Laurent
authors: Minimally Invasive Cancer Centre, Prince of Wales Hospital, Sydney, Australia.
authors: Charles
authors: C
authors: Teo
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia. b.neilan@unsw.edu.au.
authors: Brett A
authors: BA
authors: Neilan
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002922:Ciguatoxins / Q000633:toxicity*; D000087522:Cyanobacteria Toxins; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism; D012530:Saxitoxin / Q000633:toxicity*; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D017382:Reactive Oxygen Species; C001824:beta-N-methylamino-L-alanine; D002922:Ciguatoxins; D012530:Saxitoxin; D008063:Thioctic Acid; D007770:L-Lactate Dehydrogenase; C057862:cyanoginosin LR; D002118:Calcium
keywords: Cyanobacteria; Glial cells; Microcystin; Neurodegeneration; Neuroinflammation; Oxidative stress