The Potential Therapeutic Role of Thyroid Hormone in Rescuing Epigenetic Regulators Following Early Life Stress

Abstract

Adversity during early life alters neural systems and behavior, increasing susceptibility to stress in adulthood. Utilizing thyroid therapeutics, previous related research revealed connections between thyroid hormone modulations and stress response considering early life stress (ELS) and chronic social defeat stress (CSDS). Epigenetic mechanisms, active in response to ELS, were investigated here for their relationship with thyroid alterations, a poorly understood connection. Moreover, this thesis posits that rescuing thyroid regulation also rescues epigenetic regulation. By measuring relative gene expression in mice (P300, Hdac2, Kdm1a, Setdb1) across various early rearing, adult defeat, and thyroid-regulated conditions, I found decreased expression of epigenetic genes following ELS, some modulated by defeat status and others not. Additional results indicated that LT4 treatment after ELS significantly adjusted lasting gene expression. LT4 appeared to restore alterations in histone acetylation and methylation markers that are critical for neuroplasticity and stress responsiveness. Thus, while far from extensive, this investigation into four epigenetically relevant genes provides a jumping-off point for future research investigating the relationship between epigenetic regulation and thyroid therapies, with therapeutic potential.