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

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. Acknowledgment: We would like to thank the Proofreading & Editing Office of the Dean for Research at Erciyes University for copyediting and proofreading service for this manuscript.

This research was financially supported by Erciyes University Research Fund (grant number TSA-2022-11465 to Burak Tan) and by the Scientific and Technological Research Council of Türkiye (TUBITAK, grant number 220S857 to Burak Tan). Physiology Department, Faculty of Medicine, Erciyes University, Kayseri, Türkiye Burak Tan, Buse Günaydın Türker, Oğuzhan Yaylalı, Seza Nur Suluhan, Bilal Koşar, Cem Süer & Nurcan Dursun The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Tan, B., Türker, B.G., Yaylalı, O. et al. Intrahippocampal thyroid hormone administration modulates metaplasticity via Tau phosphorylation in PTU-induced hypothyroid rats.

Sci Rep (2026). https://doi.org/10.1038/s41598-026-70543-0 DOI: https://doi.org/10.1038/s41598-026-70543-0