Grant: Project Grant

Evidence suggests that women exhibit twice the risk to develop depression. Our findings from rodents indicate that innate and stress-induced changes in brain wave patterns are sex-dependent and contribute to depression-like behavioural responses. We have also shown that female, but not male, stress responses in rats are accompanied by an increase in activity of the EphA2 receptor (EphA2R) within specific brain regions, and that activation of the EphA2R in the prefrontal cortex or hippocampus regions induces depressive-like behaviour in female rats only. The EphA2R functions as an important mediator of synaptic plasticity, thus implicating the receptor as a potential candidate in the suppression of low frequency neural oscillations within the circuity that we have shown to play a key role in female-specific stress responses and depression-like risk. These studies will therefore establish a sex-specific role for the EphA2R in mediating the stress-induced structural and functional responses in brain that may contribute to depression vulnerability, and identify the receptor as a novel, and potentially female-specific, therapeutic target.