Effects of VEGF signaling on stress resilience and blood vessel density

Neurotrophic factors are known to mediate a connection between stress and stress-related disorders in limbic regions such as the prefrontal cortex (PFC) and hippocampus (HPC). In particular, Vascular Endothelial Growth Factor (VEGF) can promote angiogenesis, neurogenesis, synaptic plasticity and other functions, but its precise role as a mediator of the development of stress-related disorders remains unclear. Rats that were subjected to a 7-day social defeat paradigm and thereby found susceptible to social stress revealed higher levels of endothelia in HPC compared to resilient rats as demonstrated by elevated levels of Von Willebrand Factor (a marker of blood vessels) and endothelial glucose transporter 1. Rats subjected to a 5-day social defeat paradigm with chronic administration of pathogenic VEGF isoform VEGF₁₆₄ displayed greater stress susceptibility and less social interaction than defeated vehicle-administered controls. Taken together, these pieces of evidence suggest a potential link between VEGF and the brain architecture of stress-susceptible rats: VEGF may promote a phenotype of stress susceptibility by stimulating the development of vasculature in the brain needed to increase blood flow to the HPC, thereby increasing the anxiety experienced by the individual.