Tipping the Balance of Neural Networks: Environmental Chemicals and Autism Risk

Research into the pathophysiology and genetics of autism may inform the identification of environmental susceptibility factors that promote adverse outcomes in brain development. Conversely, understanding how low-level chemical exposure influences molecular, cellular, and behavioral outcomes relevant to the development of autism will enlighten geneticists, neuroscientists, and immunologists about autism’s complex etiologies and possibly yield novel intervention strategies. The inherent imbalances in neuronal connectivity in children at risk for autism are likely to provide the biological substrate for enhanced susceptibility to environmental triggers that are known to target signaling systems.  These systems establish the basic patterns of connectivity, from early neuronal migration and axonal pathfinding to postnatal refining of neuronal connections. Three examples of gene x environment interactions that likely contribute to autism risk are illustrated: pesticides that interfere with (1) acetylcholine  (ACh) and (2) g-aminobutyric acid (GABA) neurotransmission; and  (3) the persistent organic pollutants that directly alter Ca²⁺ signaling pathways and Ca²⁺-dependent effectors. One fundamental way in which heritable genetic vulnerabilities can amplify the adverse effects triggered by environmental exposures is if both factors (genes and environment) converge to dysregulate the same neurotransmitter and/or signaling systems at critical times during development. Recent results from studies conducted by investigators at the UC Davis Center for Children’s Environmental Health and Disease Prevention will highlight examples of gene x environment interactions relevant to autism risk. Supported by NIEHS and US EPA.