Early developmental stage glucocorticoid exposure causes DNA methylation and behavioral defects in adult zebrafish

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2022-06, Vol.256, p.109301-109301, Article 109301
• Main Authors: Xin, Ning, Wang, Da-Tong, Zhang, Li, Zhou, Yanlong, Cheng, Yanbo
• Format: Article
• Language: English
• Subjects: Animals; DNA Methylation; Female; Glucocorticoids - metabolism; Humans; Hypothalamic–pituitary–adrenal axis; Hypothalamo-Hypophyseal System - metabolism; Male; Methylation; nr3c1; Pituitary-Adrenal System; Post-traumatic stress disorder; Prednisolone - metabolism; Pregnancy; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Zebrafish; Zebrafish - genetics; Zebrafish - metabolism
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2022.109301

Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by genetic and environmental factors. It is closely related to a dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, in which the epigenetic modification of the nr3c1 plays an important role. It is well known that nr3c1 methylation in offspring is reportedly related to early adverse life experiences, prenatal stress response, and early nursing conditions; however, the methylation location and extent of the nr3c1 are not sufficiently elucidated. In order to study the internal mechanism of PTSD caused by early adverse life experience, we used zebrafish to construct a psychopathological model. We found that early developmental stage prednisolone exposure caused HPA axis negative feedback dysfunction and hormone secretion disorder in adult male zebrafish. By analyzing nr3c1 promoter, we found that cytosine-guanine island (CpGI) 2 was highly methylated in adult male zebrafish, which affected the expression of glucocorticoid receptor, resulting in abnormal behavior and anxiety like phenotype of adult male zebrafish. Therefore, we believed that an early exposure of zebrafish larvae to prednisolone may be recorded through a change of CpGI 2 methylation in the nr3c1 promoter region, causing abnormal adult male zebrafish behavior. Moreover, the establishment of the zebrafish psychopathological model may facilitate the study of the clinical management of patients with PTSD. [Display omitted] •Early zebrafish prednisolone exposure impedes the negative feedback function of the HPA axis.•Early prednisolone-exposed adult male zebrafish have similar anxiety and avoidance features.•The zebrafish is a psychopathological model for patients with post-traumatic stress disorder.