I.N. Pessah, Dept. Molecular Biosciences, Univ. California, Davis, CA 95616
There is growing concern from both parents and health professionals that prenatal and postnatal exposure to xenobiotic mixtures ( e.g. mercurials, halogenated aromatics, and pesticides) and biotic ( e.g. vaccine antigens) factors may act synergistically to alter the penetrance of as yet unidentified genetic factors conferring susceptibility to autism. Non-coplanar polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) are major co-contaminants of human food, and ethyl mercury has been used in high levels as vaccine preservatives. Both contaminants have been causally linked to behavioral and developmental deficits in infants, though virtually nothing is known about their influence on regions of the brain important to development of social behavior. We have investigated the molecular mechanisms by which non-coplanar PCBs and thimerosal alter temporal and spatial aspects of Ca2+ signaling in primary neurons and neurogenic cell lines. Non-coplanar PCBs (100 nM-10 mM) alter Ca2+ signaling by selective modulation of the immunophilin FKBP12/ryanodine receptor (RyR) complex whereas thimerosal alters the redox-sensing properties of Ca2+-release units. These contaminants, in combination, act synergistically to alter the fidelity of Ca2+ signals important for growth and development of dendritic processes. The implications of these finding as possible risk factors in autism will be discussed.
Back to Agenda