Phan, Tram-Anh Ngoc

Humans subjected to childhood trauma are more likely to develop anxiety disorders such as post-traumatic stress disorder, yet how Early-Life-Stress (ELS) impacts the function, or the development of the nervous system remains poorly understood. We developed a zebrafish model of ELS. Because of the powerful genetics and accessibility to the brain, the zebrafish is an excellent system to explore how ELS alters brain development and function. The neuroendocrine stress system in zebrafish is mediated in part by the hypothalamic–pituitary–interrenal (HPI) axis, which is analogous to mammalian hypothalamic—pituitary—adrenal (HPA) axis. When perceiving stress, the zebrafish hypothalamus releases corticotropin-releasing hormone, which signals to the pituitary gland to release adrenocorticotropic releasing hormone (acth). Acth then signals down to the interrenal gland, which in-turn secretes cortisol. Cortisol then binds to glucocorticoid and mineralocorticoid receptors in the brain, to mediate stress responses and inhibit the HPA/HPI. We hypothesize that in zebrafish larvae that the ELS may alter the relative expression of genes in the HPI pathway. We generated ELS zebrafish larvae and measured the relative expression levels of corticotropic releasing hormone (crh), glucocorticoid receptor (gr), and mineralocorticoid receptor (mr). We find that the level of expression of crh is modestly higher in ELS zebrafish, which is consistent with higher levels of stress. Moreover, the expression level of gr is higher in ELS zebrafish, while no significant differences in the expression level of mr were found. This data suggests that ELS may disrupt the normal gr:mr ratio in zebrafish subjected to ELS. We are following up on these studies by localizing which neuronal regions are most affected via in situ hybridization.