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Age effect on thyroid hormone brain response in male mice

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Abstract

Purpose

Thyroid hormones (TH) are important for brain development and central nervous system (CNS) function. Disturbances of thyroid function occur with higher prevalence in the ageing population and may negatively impact brain function.

Methods

We investigated the age impact on behavior in young adult and old male mice (5 vs. 20 months) with chronic hypo- or hyper-thyroidism as well as in sham-treated controls. Expression of TH transporters and TH responsive genes was studied in CNS and pituitary by in situ hybridization and qRT-PCR, whereas TH serum concentrations were determined by immunoassay.

Results

Serum TH levels were lower in old compared with young hyperthyroid mice, suggesting a milder hyperthyroid phenotype in the aged group. Likewise, elevated plus maze activity was reduced in old hyperthyroid animals. Under hypothyroid conditions, thyroxine serum concentrations did not differ in young and old mice. Both groups showed a comparable decline in activity and elevated anxiety levels. However, an attenuated increase in hypothalamic thyrotropin releasing hormone and pituitary thyroid stimulating hormone transcript expression was found in old hypothyroid mice. Brain expression of monocarboxylate transporter 8 and organic anion transporting polypeptide 1c1 was not affected by age or TH status.

Conclusions

In summary, ageing attenuates neurological phenotypes in hyperthyroid but not hypothyroid mice, which fits with age effects on TH serum levels in the animals. In contrast no changes in TH transporter expression were found in aged mouse brains with hyper- or hypo-thyroid state.

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Acknowledgements

The authors are grateful to A. Jaeger, S. Rehn, M. Schmidt for their dedicated technical support.

Funding

This work was supported by DFG FU356/7–1/2 to DF, MO1018/2–1/2 to LCM, and HE3418/8–1 to HH in the framework of SPP1629 and RTG1715 to HH/FK. Funding source was not involved in decisions about study design; collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Author notes

  1. These authors contributed equally: Frederike Kramer and Denica Doycheva

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122, Essen, Germany

    Helena Kerp, Kathrin Engels, Georg Sebastian Hönes, Denise Zwanziger, Lars Christian Moeller, Heike Heuer & Dagmar Führer

  2. Leibniz Institute on Aging/Fritz Lipmann Institute (FLI), 07745, Jena, Germany

    Frederike Kramer, Denica Doycheva & Heike Heuer

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  1. Helena Kerp
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Correspondence to Dagmar Führer.

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The authors declare that they have no conflict of interest.

Ethical approval

All animal experiments were performed in accordance with the German regulations for Laboratory Animal Science (GVSOLAS) and the European Health Law of the Federation of Laboratory Animal Science Associations (FELASA). The protocols for animal studies were approved by the Landesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen (LANUV-NRW), Germany (AZ.84–02.04.2013.A188).

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Kerp, H., Engels, K., Kramer, F. et al. Age effect on thyroid hormone brain response in male mice. Endocrine 66, 596–606 (2019). https://doi.org/10.1007/s12020-019-02078-6

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