Role of RAS/RAF/ERK pathway in pathogenesis and treatment of autism

Animal models offer opportunities to conduct biological studies in order to identify the mechanisms responsible for autism symptoms. Researchers commonly use the BTBR mouse strain as a model for studying mechanisms that may be responsible for the development of autism, because BTBR mice show many autism-like behaviors.

Growing evidence suggests that an important signaling pathway in the cells, the RAS/RAF/ERKl/2 pathway, plays a role in promoting programmed cell death in neural cells and in the genesis of neural progenitors, learning and memory. Mutations in chromosome 16, which includes the MAPKJ gene that encodes ERK1, have been associated with autism.

Xiaohong Li and her colleagues at the New York State Institute for Basic Research in Developmental Disabilities began with the hypothesis that the alteration of ERKl/2 signaling activity could be crucially involved in the pathogenesis of autism and that manipulation of this pathway could be a promising avenue for therapeutic interventions. They investigated the developmental and spatial pattern of ERKl/2 signaling in the BTBR mouse brain.

They found that the activities of ERKl/2 signaling are enhanced in the brain of newborn BTBR mice. However, as the mice aged, the enhanced ERKl/2 activity gradually subsided to a normal level. In further studies, the researchers used an inhibitor to decrease the activity of ERKl/2 signaling in BTBR mice. This treatment helped to reduce autism-like behaviors in BTBR mice, such as impaired social interactions.