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Neurotoxic Effects of Microbial Toxins
Principal investigator: Prof. Kai Savolainen, MD, PhD, Finnish Institute of Occupational Health, Industrial Hygiene and Toxicology, e-mail: kai.savolainen@occuphealth.fi

In Finland, half of all homes have a moisture problem, and microbial growth occurs in 20 percent of the cases. Altogether 500 000 individuals are annually exposed to indoor bioaerosols. Recent evidence suggests that this exposure may cause CNS effects in addition to adverse effects in the respiratory system. In fact, adverse CNS effects after exposure to bioaerosols, i.e. bacteria, fungi, molds, microbial cell wall components or metabolic products of microbes, have been found in experimental animals and humans. Available evidence indicates that both neuronal and glial cells can be affected by this exposure. The effects of microbial toxins on the CNS are of particular importance because even a small excess morbidity of brain diseases may imposes a major burden on the health care system and the society at large. The focus of this research is to increase understanding of the role of microbial toxins in bioaerosol-induced CNS health effects. The overall objective is to study the mechanisms whereby LPS, and toxins of Fusarium multiforme, fumonisin B1, and of Stachybotrus chartarum (trichothecenes) activate neuronal and glial cells. The specific aims: 1. To study cell activation by the toxins; 2. To study altered gene expression by these toxins; 3. to study mechanisms of apoptosis induced by these toxins; and 4. to explore the role of cytokine production in the effects of these toxins. Methods: ROS and NO production will be studied with a fluorescent probe, and photometrically. Cell death will be analysed fluorometrically, and apoptosis with DNA fragmentation and with a fluorescent probe. Transcription factor binding will be studied with an EMSA assay, and cytokine production with an ELISA assay. Expression of iNOS is explored at protein, and of an apoptosis promoter BAX, and an antiapoptotic gene Bcl-2, at mRNA level. Also caspase expression (mRNA level) and activity will be studied. We expect that the proposed studies will provide valuable information of the mechanisms of effects of microbial toxins in neuronal and glial cells. This information can be utilized in assessing health hazard of bioaerosol exposure, and in evaluating the need of human epidemiological studies.