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Abstract #2235

Pharmacological Inhibition of ERK Pathway Rescues Morpho-Anatomical Aberrancies Associated with 16p11.2 Chromosomal Deletion

Marco Pagani1,2, Joanna Pucilowska3, Camilla Robol1, Joseph Vithayathil3, Caitlin Kelly3, Colleen Karlo3, Riccardo Brambilla4, Gary E. Landreth3, and Alessandro Gozzi1

1Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy, 2CIMeC, Center for Mind/Brain Sciences, University of Trento, Rovereto, Italy, 3Department of Neurosciences, Case Western Reserve University, Cleveland, OH, 4School of Biosciences, Cardiff University, Cardiff, United Kingdom

16p11.2 microdeletion is the most common copy number variation in autism. Recent studies revealed that mice harboring this microdeletion exhibit a paradoxical elevation of ERK activity, macroscale gray matter abnormalities and autistic-like behavioral deficits. By using high-resolution morpho-anatomical MRI, we show that prenatal treatment with an ERK pathway inhibitor rescues hippocampal and septal anatomical deficits in 16p11.2del mutants. The effect was associated with amelioration of anxiety behaviors. These results provide the first example of the rescue of developmental gray matter abnormalities in this mouse model, and support the translational use of structural MRI to assess putative therapeutic effects in autism.

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