To study the autism-related effects of this protein fragment on postnatal neurodevelopment and behavior, Dr. Tan and his team inserted the human DNA sequence coding for the sAPP-α fragment into the genome of a mouse model for autism. While the studies are ongoing, the researchers documented the protein fragment's effects on the immune system of the test mice.
"We used molecular biology and immunohistochemistry techniques to characterize T-cell development in the thymus and also function in the spleen of the test animals," Dr. Tan said. "Then we compared transgenic mice to their wild-type littermates."
The researchers found that increased levels of sAPP-α in the transgenic mice led to increased cytotoxic T-cell numbers. The investigators also discovered subsequent impairment in the recall function of memory T-cells in the test mice, suggesting that the adaptive immune response is negatively affected in the presence of high levels of the protein fragment.
"Our work suggests that the negative effects of elevated sAPP-α on the adaptive immune system is a novel mechanism underlying certain forms of autism," concluded Dr. Tan, who holds the Silver Chair in Developmental Neurobiology. "The findings also add support to the role of sAPP-α in the T-cell response."
|Contact: Anne DeLotto Baier|
University of South Florida (USF Health)