We previously discovered that subjects with idiopathic autism have reduced levels of TrkB and TrkB signaling in their brains. Valproic acid exposure in utero also reduces TrkB signaling in rodents and produces autistic behaviour in humans and mice. We used a small molecule agonist of TrkB in these mice to increase TrkB signaling, and this eliminated the sociability deficits and repetitive behaviour typical of autism. We are currently exploring whether this agonist also eliminates spine (synaptic) deficits.
Impact
This work confirms the contribution of the TrkB signaling pathway to autistic behaviour, providing valuable information on the molecular mechanisms underlying autism. It also demonstrates that autistic behaviour arising from a prenatal exposure can be eliminated in young adult animals, and suggests that TrkB agonists might be used therapeutically to treat certain types of autism.
Student Experience
My graduate student, Chiara Nicolini, was responsible for this project as part of her PhD thesis work. She carried out the experiments, analyzed the data and wrote the paper. She was aided in some of the data collection and analysis by several undergraduate students who performed their undergraduate projects or honours theses under Chiara’s guidance.
