The Simons Foundation for Autism Research (SFARI) awarded a new a grant to be laboratory led by Dr. Maria Domercq to study the impact of myelin in autism spectrum disorders (ASD)
With a budget of $300,000 the project will test the therapeutic potential of boosting myelination during development to improve behavioral alterations in an animal model of ASD.
The Simons Foundation for Autism Research (SFARI) has awarded a $300000 grant to ACHUCARRO, for a collaboration project led by the laboratory of Dr. María Domercq. The two-year project will start in 2023 and strives to boost myelination in animal models of autism spectrum disorders (ASD).
During development, brain is characterized by critical periods of experience-dependent remodeling of neuronal circuits and failure to end these periods results in neurodevelopmental disorders such as autism spectrum disorders (ASD). Two leading hypothesis for the pathophysiology in ASD are abnormal neuronal connectivity and imbalances in excitation/inhibition. Recently, a convergent molecular pathway was identify by integrative transcriptomic analysis in seven mouse animal models as well as in human postmortem brain samples from ASD people (Phan et al., 2020. Nat. Neurosci. 23:375). These results implicate disruption in oligodendrocyte development and myelination as a cellular mechanism in ASD pathology. However, the etiology of myelin deficits as well as the therapeutic potential of strategies promoting myelination in ASD is practically unknown.
The laboratory led by Dr María Domercq hypothesize that modulation of myelination could reverse myelin deficits, PV+ interneuron survival and behavior alterations in ASD mice. The hypothesis will be tested using an animal model of ASD, mice deficient in cntnap gene that codifies for Contactin-associated protein-2 (Caspr2), characterized by Dr. Olga Peñagarikano (UPV/EHU), a key collaborator in this project. The team will use chemogenetics to boost the brain myelination capacity and improve impaired myelination in this ASD model. Data obtained from this proposal will contribute to reveal new mechanisms involved in ASD pathogenesis, and to validate a novel intervention strategies based on plastic myelination promotion.