The mechanisms of neurotoxicity induced by a Stachybotrys chartarum tichothecene mycotoxin in an in vitro model
Sick-building syndrome (SBS) is a phenomenon in which individuals in buildings with poor indoor air quality (IAQ) experience health problems associated with the environment of the building. Fungal contamination in buildings due to species such as Stachybotrys chartarum and Penicillium chrysogenum has been correlated to poor IAQ. Symptoms experienced by individuals exposed to mycotoxins produced by Stachybotrys species include, headaches, fatigue, nausea, vomiting, bleeding from mucosal membranes, depression, sleep disturbances, anxiety, vertigo, memory-loss and seizures. Although these symptoms have been observed in individuals exposed to Stachybotrys sp. mycotoxins, the mechanisms by which these compounds may contribute to neurotoxicity are unknown. In this study, a series of experiments were conducted on human brain-capillary endothelial cells (HBCEC), astrocytes, and progenitor neuronal cells. The purpose of this study was to evaluate the effects induced by satratoxin H on neural tissues; this includes the HBCEC which forms the blood-brain barrier, followed by the astrocytes which act as immune cells, and the neurons. These cell lines were exposed to satratoxin H at concentrations ranging from 1ng/ml to 5000ng/ml. These data were compared to controls; cells exposed to known inflammatory compounds such as lipopolysaccharide (LPS), cells exposed to oxidative stress induced by hydrogen peroxide (H202), and to both LPS and H202 with satratoxin H. Immunofluorescent examination was used to evaluate apoptosis events, and the expression of cellular receptors including. Supernatants and cellular extracts were examined for inflammatory agents as well as compounds associated with apoptosis. The results of these studies demonstrated that at satratoxin H concentrations (1ng/ml- 10ng/ml), results were similar to control cells, while cells exposed to moderate concentrations of 100ng/ml-1000ng/ml of satratoxin H alone or with LPS or H202, demonstrated high expression of inflammatory and apoptotic events. These experiments demonstrate that the macrocyclic trichothecenes produced by Stachybotrys chartarum are able to induce apoptotic and inflammatory cascades in endothelial cells, astrocytes, and neurons. These studies suggest that exposure to low to moderate doses of satratoxin could activate cellular pathways that induce a series of events leading to neurological tissue damage, which may induce the symptoms observed in individuals exposed to Stachybotrys chartarum.