title: Mapk/Erk activation in an animal model of social deficits shows a possible link to autism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We evaluated Mapk/Erk1/2, cellular proliferation and apoptosis in BTBR mice, as a preclinical model of Autism. We had previously generated 410 F2 mice from the cross of BTBR with B6. At that time, six different social behaviors in all F2 mice were evaluated and scored. In this study, eight mice at each extreme of the social behavioral 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 mice, testing for correlation in the degree of kinase activation across these separate tissues.
  
  
  RESULTS
  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 (p-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 for this signaling pathway.
  
  
  CONCLUSIONS
  These observations suggest that 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 central nervous system (CNS) ERK activity, and possibly autistic behavior.
authors: Department of Neurology, University of California, 675 Nelson Rising Way, Suite 214B, San Francisco, CA 94158 USA ; Methodist Neurological Institute, 6550 Fannin St, Houston Texas, 77030 USA.
authors: Alireza
authors: A
authors: Faridar
authors: Department of Neurology, University of California, 675 Nelson Rising Way, Suite 214B, San Francisco, CA 94158 USA.
authors: Dorothy
authors: D
authors: Jones-Davis
authors: Department of Neurology, University of California, 675 Nelson Rising Way, Suite 214B, San Francisco, CA 94158 USA.
authors: Eric
authors: E
authors: Rider
authors: Department of Neurology, University of California, 675 Nelson Rising Way, Suite 214B, San Francisco, CA 94158 USA.
authors: Jiang
authors: J
authors: Li
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072 Australia.
authors: Ilan
authors: I
authors: Gobius
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072 Australia.
authors: Laura
authors: L
authors: Morcom
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072 Australia ; School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072 Australia.
authors: Linda J
authors: LJ
authors: Richards
authors: Epidemiology and Biostatistics, University of California, 550 16th Street, San Francisco, CA 94158 USA.
authors: Saunak
authors: S
authors: Sen
authors: Department of Neurology, University of California, 675 Nelson Rising Way, Suite 214B, San Francisco, CA 94158 USA.
authors: Elliott H
authors: EH
authors: Sherr