Increased anxiety and fear memory in adult mice lacking type 2 deiodinase

Always dangerous to take evidence from mice into men, but even the abstract suggests that this research could provide some insight.

Further, anxiety seems undoubtedly to be an important issue in thyroid disorders.

If reduced T3 content of the brain can lead to elevated anxiety, have you any idea what we could do to reduce anxiety? Surely it couldn't be another reason to consider liothyronine (T3) as an important medicine, could it? Another reason outside traditional endocrinology.

Psychoneuroendocrinology. 2017 Jun 16;84:51-60. doi: 10.1016/j.psyneuen.2017.06.013. [Epub ahead of print]

Increased anxiety and fear memory in adult mice lacking type 2 deiodinase.

Bárez-López S1, Montero-Pedrazuela A2, Bosch-García D3, Venero C4, Guadaño-Ferraz A5.

Author information

1 Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols'', Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Arturo Duperier, 4, 28029, Madrid, Spain; Department of Endocrine, U-708, Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos III, Madrid, Spain.

2 Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols'', Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Arturo Duperier, 4, 28029, Madrid, Spain.

3 Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols'', Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Arturo Duperier, 4, 28029, Madrid, Spain.

4 Department of Psychobiology, Universidad Nacional de Educación a Distancia, Juan del Rosal 10, 28040, Madrid, Spain. Electronic address: cvenero@psi.uned.es.

5 Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas "Alberto Sols'', Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Arturo Duperier, 4, 28029, Madrid, Spain; Department of Endocrine, U-708, Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with increased anxiety-like behavior as well as enhanced auditory-cued fear memory and spontaneous recovery of fear memory following extinction. D2KO mice also presented reduced T3 content in the hippocampus and decreased expression of the T3-dependent gene Dio3 in the amygdala suggesting a hypothyroid status in this structure. We propose that the emotional dysfunctions found in D2KO mice can arise from the reduced T3 content in their brain, which consequently leads to alterations in gene expression with functional consequences. We found a downregulation in the gene encoding for the calcium-binding protein calretinin (Calb2) in the amygdala of D2KO mice that could affect the GABAergic transmission. The current findings in D2KO mice can provide insight into emotional disorders present in humans with DIO2 polymorphisms.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

Adult brain; Amygdala; Emotional disorders; Learning and memory; Thyroid hormones; Type 2 deiodinase

PMID: 28654773

DOI: 10.1016/j.psyneuen.2017.06.013

ncbi.nlm.nih.gov/pubmed/286...

Full paper is behind Elsevier's paywall.

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  • Thanks @helvella. This is great. Another argument to support my need for T3 as I have faulty gene DIO2. No wonder I feel improved psychological wellbeing since I started taking it just over a year ago.

  • Very interesting, thanks for info.

    As I have real problems with anxiety that only became this bad towards the later stages of hypothyroidism and which have stubbornly persisted on treatment, with only minor improvements on NDT; I wondered if the 23&me raw data can be used to discover if you are lacking type 2 deiodinase. I have a vague recollection of a comment in a post here of it not being adequate for this purpose.

  • Thank you for this brilliant piece of research about t3 and the impact of D2-deficiency.

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