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A role for immune molecules in cortical connectivity: potential implications for autism

State/Province Full: 
United States

Autism is a pervasive developmental disorder resulting from altered brain development and connectivity. It is thought that defects in synapse formation cause improper wiring in the brain, resulting in the cognitive and behavioral deficits typical in autism. The formation of synapses—synaptogenesis—is a very complex process. Only two proteins are currently known to decrease the number of these connections during early brain development. Interestingly, one of these proteins, the major histocompatibility complex class I (MHCI), happens to be very important in regulating the immune response while also being able to inhibit the establishment of synapses in the brain. The other protein, myocyte enhancer factor 2 (MEF2), is required for normal brain development and alters the expression of genes that are linked to autism. The fellow proposes to use molecular biology and biochemical techniques to alter the function of MHCI and MEF2 in brain cells to probe the molecular pathway underlying their function. One of the most common themes among the environmental factors thought to lead to autism is their ability to activate the immune system. By defining the relationship between these two proteins with respect to synapse formation, this study will help us better understand how the immune system could alter connections in the developing brain to give rise to neurodevelopmental disorders. Most importantly, results from our work could identify novel drug targets for treating diseases that are influenced by immune dysregulation, such as autism.