aberrant immune responses in a mouse with behavioral disorders异常的免疫反应在鼠标行为障碍.pdfVIP

Aberrant Immune Responses in a Mouse with Behavioral Disorders 1. 2,3. 2 2 2,3 Yong Heo , Yubin Zhang , Donghong Gao , Veronica M. Miller , David A. Lawrence * 1 College of Natural Sciences, Catholic University of Daegu, Kyongsan-si, Republic of Korea, 2 Wadsworth Center, New York State Department of Health, Albany, New York, United States of America, 3 University at Albany School of Public Health, Albany, New York, United States of America Abstract BTBR T+tf/J (BTBR) mice have recently been reported to have behaviors that resemble those of autistic individuals, in that this strain has impairments in social interactions and a restricted repetitive and stereotyped pattern of behaviors. Since immune responses, including autoimmune responses, are known to affect behavior, and individuals with autism have aberrant immune activities, we evaluated the immune system of BTBR mice, and compared their immunity and degree of neuroinflammation with that of C57BL/6 (B6) mice, a highly social control strain, and with F1 offspring. Mice were assessed at postnatal day (pnd) 21 and after behavioral analysis at pnd70. BTBR mice had significantly higher amounts of serum IgG and IgE, of IgG anti-brain antibodies (Abs), and of IgG and IgE deposited in the brain, elevated expression of cytokines, especially IL-33 IL-18, and IL-1b in the brain, and an increased proportion of MHC class II-expressing microglia compared to B6 mice. The F1 mice had intermediate levels of Abs and cytokines as well as social activity. The high Ab levels of BTBR mice are in agreement with their increased numbers of CD40hi/I-Ahi B cells and IgG-secreting B cells. Upon immunization with KLH, the BTBR mice produced 2–