Knowledge Bank

The current, primary treatments for anxiety disorders, which constitute most mental health diagnoses in the United States, have many significant side effects and may even increase suicidality in pre-adolescent people (ADAA, 2018). The ever-evolving need for new treatments has led to the exploration of stem cells and their potentially therapeutic secretomes. Vascular endothelial growth factor (VEGF) has been shown to modulate anxiety-like behavior in rodents, though the source of this VEGF is yet to be investigated. Neural stem cells (NSCs) are also known to modulate anxiety via upregulation of neurogenesis in the ventral hippocampus (Hill et, al., 2015), and VEGF has been recently identified as a protein of the NSC secretome (Denninger, et, al., 2020). In this study, I focused on the ventral hippocampal neurogenic niche, a region of the brain which in known to be involved in regulating affective behavior (Calhoon, et, al., 2020). I used a transgenic mouse line which allowed for the inducible knockdown of neural stem cell (NSC)-derived vascular endothelial growth factor (VEGF). Using adult mice, I conducted open field (OF) and elevated plus maze (EPM) tests to determine whether VEGF-KD in NSCs in adulthood acutely modulates anxiety-like behavior, which revealed an anxiolytic impact of VEGF-KD. Analysis of immunohistochemistry (IHC) also revealed a potential paracrine effect on the excitability of the circuit of ventral SGZ, as VEGF-KD resulted in decreased neuronal activation in this hippocampal layer compared to control mice. These findings may lead to translational application in the field of stem-cell mediated therapies, more specifically to those which involve harnessing the secretome of these cells.