Evidence for thyroid hormone regulation of amygdala-dependent fear-relevant memory and plasticity.

Autor: Maddox SA; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Ponomareva OY; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Zaleski CE; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA.; Northeastern University, Boston, MA, USA., Chen MX; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA.; University of Iowa, Iowa City, IA, USA., Vella KR; Joan and Sanford I. Weill Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, New York, NY, USA.; Weill Center for Metabolic Health, Weill Cornell Medicine, New York, NY, USA., Hollenberg AN; Joan and Sanford I. Weill Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, New York, NY, USA.; Weill Center for Metabolic Health, Weill Cornell Medicine, New York, NY, USA., Klengel C; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA., Ressler KJ; Neurobiology of Fear Laboratory, Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA. kressler@mclean.harvard.edu.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. kressler@mclean.harvard.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1038/s41380-024-02679-2
Abstrakt: The amygdala is an established site for fear memory formation, and clinical studies suggest involvement of hormone signaling cascades in development of trauma-related disorders. While an association of thyroid hormone (TH) status and mood disorders is established, the related brain-based mechanisms and the role of TH in anxiety disorders are unknown. Here we examine the role that TH receptor (TR, a nuclear transcriptional repressor when unbound and a transcriptional activator when bound to TH) may have in mediating the initial formation of fear memories in the amygdala. We identified mRNA levels of TR and other TH pathway regulatory genes, including thyrotropin-releasing hormone (Trh), transthyretin (Ttr), thyrotropin-releasing hormone receptor (Trhr), type 2 iodothyronine deiodinase (Dio2), mediator complex subunit 12 (Med12/Trap230) and retinoid X receptor gamma (Rxrg) to be altered in the amygdala following Pavlovian fear conditioning. Using TH agonist and antagonist infusion into the amygdala, we demonstrated that this pathway is both necessary and sufficient for fear memory consolidation. Inhibition of TH signaling with the TR antagonist 1-850 decreased fear memory consolidation; while activation of TR with T3 (triiodothyronine) resulted in increased memory formation. Using a systemic hypothyroid mouse model, we found that intra-amygdala infusions of T3 were sufficient to rescue deficits in fear memory. Finally, we demonstrated that T3 was sufficient to activate TR-specific gene pathways in the amygdala. These findings on the role of activity-dependent TR modulation support a model in which local TH is a critical regulator of fear memory-related plasticity in the amygdala.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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