Intrahippocampal thyroid hormone administration modulates metaplasticity via Tau phosphorylation in PTU-induced hypothyroid rats

Abstract

Abstract This study investigates the influence of thyroid hormones—triiodothyronine (T3) and thyroxine (T4)—on hippocampal metaplasticity and Tau phosphorylation under hypothyroid conditions. Employing electrophysiological assessments and biochemical analyses, we demonstrate that T3 enhances metaplasticity, an effect associated with the restoration of Akt signaling pathway activity, and mitigates excessive Tau phosphorylation associated with hypothyroidism. In contrast, while T4 reduces Tau phosphorylation, it fails to enhance metaplasticity, likely because its conversion to the active form, T3, is delayed. These findings suggest that T3 plays a critical role in modulating synaptic plasticity mechanisms underlying learning and memory and may serve as a promising therapeutic agent in neurodegenerative disorders. The study underscores the potential role of thyroid hormone regulation in ameliorating hippocampal dysfunction and opens avenues for future research on its impact in conditions such as Alzheimer’s disease.