title: Impact of fumonisin B1 on glutamate toxicity and low magnesium-induced seizure activity in neuronal primary culture.
abstract: Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. mould that contaminates maize world-wide. Although its neurodegenerative potential is well established, mechanisms and acute effects of FB(1) on neurons are still not completely understood. Our previous study on astrocytes and neuroblastoma cells demonstrated that acute FB(1) exposure inhibits mitochondrial complex I and leads to mitochondrial membrane potential depolarization and calcium deregulation. To further explore the mechanisms of FB(1) neurotoxicity, we here investigated the effects of acute FB(1) co-exposure with glutamate and in the low magnesium model of epilepsy on neuronal calcium level, mitochondrial membrane potential, and cell death in glio-neuronal cultures. FB(1) increased the glutamate-induced calcium signal in neurons and changed neuronal calcium signals to more sustained intracellular calcium rises in the low magnesium model of epilepsy that coincided with mitochondrial membrane potential depolarization. FB(1) co-exposure increased the percentage of dead neurons in low magnesium conditions dose dependently when compared with low magnesium exposure only, whereas in FB(1) and glutamate co-exposure neuronal death remained unchanged when compared with glutamate treatment only. Our results show that FB(1) makes neurons more vulnerable to glutamate-induced toxicity and epileptiform conditions, indicating that FB(1) can enhance the detrimental effect of these conditions on neurons.
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK. adomijan@pharma.hr
authors.forename: A-M
authors.initials: AM
authors.lastname: Domijan
authors.forename: S
authors.initials: S
authors.lastname: Kovac
authors.forename: A Y
authors.initials: AY
authors.lastname: Abramov
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D018920:Coculture Techniques; D003470:Culture Media; D037341:Fumonisins / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D008275:Magnesium Deficiency / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*
chemical_list: D003470:Culture Media; D037341:Fumonisins; D009183:Mycotoxins; D018698:Glutamic Acid; C056933:fumonisin B1