Mapk/Erk activation in an animal model of social deficits; a possible link to autism (P2.226)

Objective There is converging preclinical and clinical evidence to suggest that the extracellular signal regulated kinase (ERK) signaling pathway may be dysregulated in autism spectrum disorders.Method: We evaluated MAPK/Erk1/2, cellular proliferation and apoptosis in BTBR mice, as a preclinical model of Autism. We also generated 410 F2 mice from the cross of BTBR with B6. We evaluated and scored six different social behaviors in all F2 mice. Eight mice at each extreme of the social behavior spectrum were selected and the expression and activity levels of Mapk/Erk in the prefrontal cortex and cerebellum of these mice were compared. Finally, we compared the Mapk/Erk signaling pathway in brain and lymphocytes of the same miceResults: Levels of phosphorylated Erk (p-Erk) were significantly increased in the brains of BTBR versus control mice. We also observed a significant association between juvenile social behavior and phosphorylated mitogen-activated protein kinase kinase (Mek) and p-Erk levels in the prefrontal cortex but not in the cerebellum. In contrast, we did not find a significant association between social behavior and total protein levels of either Mek or Erk. We also tested whether steady-state levels of Erk activation in the cerebral cortex in individual animals correlated with levels of Erk activation in lymphocytes, finding a significant relationship in this signaling pathway.Conclusion: Dysregulation of the Erk signaling pathway may be an important mediator of social behavior and that measuring activation of this pathway in peripheral lymphocytes may serve as a surrogate marker for human CNS ERK activity and possibly autistic behavior. Disclosure: Dr. Faridar has nothing to disclose. Dr. Jones-Davis has nothing to disclose. Dr. Rider has nothing to disclose. Dr. Li has nothing to disclose. Dr. Gobius has nothing to disclose. Dr. Marcom has nothing to disclose. Dr. Richards has nothing to disclose. Dr. Sherr has nothing to disclose.