- Awarded: 2017
- Award Type: Explorer
- Award #: 555504
Oxytocin is being proposed as a treatment for autism and anxiety, but its use has limited potential until mechanisms of oxytocin action in the brain are better understood. Moses Chao and his colleagues have gathered preliminary evidence showing a link between oxytocin signaling and the brain-derived neurotrophic factor (BDNF) tropomycin receptor kinase B (TrkB) receptor. Oxytocin rapidly transactivates TrkB receptors without BDNF in acute brain slices of 2-week-old mice and in primary neuronal cultures. This transactivation event occurs in the cortex within 15 minutes of oxytocin treatment and is dose dependent. These findings suggest that oxytocin may utilize downstream TrkB signaling for its actions. Chao now proposes to investigate the role of oxytocin receptor signaling in facilitating information processing through receptor crosstalk. This work will give insights into the basic molecular mechanisms of oxytocin and its receptors, which are relevant to autism, anxiety and social behavior.
Chao’s project will focus on the signaling properties of the oxytocin receptor and how neurotrophin-related pathways may be involved. He hypothesizes that oxytocin can signal through TrkB receptors through receptor transactivation. To determine if the long-term effects of oxytocin are due to signaling through the TrkB receptor, Chao’s team proposes to use an unbiased mass spectrometric Tandem Mass Tag technique, a new and powerful tool for quantitative proteomics across multiple conditions and time points. They will use this strategy to identify protein and phosphorylation changes downstream of oxytocin and assess if those are BDNF dependent. Changes in proteins after transactivation may reflect proteomic events downstream of BDNF-TrkB signaling.
Because of its pro-social effects on maternal care, affiliation and social attachment, oxytocin has been a focus of therapeutic effects in autism spectrum disorders. Very little is known about how the oxytocin receptor transduces its signals in the brain to generate its physiological and behavioral effects. Chao’s exploratory project will provide molecular insights into downstream events of the oxytocin receptor.