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Bipolar limbic expression of auto-immune thyroid targets: thyroglobulin and thyroid-stimulating hormone receptor

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Abstract

The associations between thyroid auto-immunity and neuro-psychiatric disorders are well-documented. However, there exists limited literature specifically linking auto-immune thyroid disease (AITD) to bipolar disorder (BD). Thus, we investigated the likely association between Hashimoto’s disease and BD through the extra-thyroidal localisation of thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in limbic regions of normal and bipolar human adult brain. Further, we hypothesised that changes in thyroid expression in bipolar limbic cortex may contribute to mood dysregulation associated with BD. Immuno-chemistry and in-situ PCR were used to localise TSH-R/TG within the amygdala, cingulate gyrus and frontal cortex of normal (n = 5) and bipolar (n = 5) brains. Reverse-transcriptase qPCR provided fold-change differences in TSH-R gene expression. The results demonstrated reduced thyroid protein expression in bipolar limbic regions; these novel results correlate with other neuro-imaging reports that describe reduced cortico-limbic tissue volumes and neuro-physiological activity during BD. We also demonstrated TG-like proteins exclusive to bipolar amygdala neurons, and which relates to previous neuro-imaging studies of amygdala hyperactivity and enhanced emotional sensitivity in BD. Indeed, reduced TSH-R/TG in limbic regions may predispose to, or bear relevance in the pathophysiology of mood dysregulation and symptoms of BD. Further, we attribute mood dysregulation in BD to limbic-derived TSH-R, which probably provides potential targets for thyroid auto-immune factors during Hashimoto’s disease. Consequently, this may lead to inactivated and/or damaged neurons. The neuro-pathology of diminished neuronal functioning or neuronal atrophy suggests a novel neuro-degeneration mechanism in BD.

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Abbreviations

TH:

thyroid hormones

TSH-R:

thyroid-stimulating hormone receptor

TRH:

thyrotropin-releasing hormone

TG:

thyroglobulin

AITD:

auto-immune thyroid disease

FFPE:

formalin-fixed paraffin-embedded

BD:

bipolar disorder

DAB:

diaminobenzidine

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Acknowledgements

The authors thank Kogie Moodley from the School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal for providing technical assistance, and Cathy Connelly from the Biostatistics Unit, Department of Family Medicine and Public Health, University of KwaZulu-Natal for providing statistical assistance.

Funding

The study was funded by the College of Health Sciences, University of KwaZulu-Natal and Medical Research Council of South Africa.

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  1. Therapeutics and Medicines Management, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Private bag X7, Durban, 4001, South Africa

    Meleshni Naicker & Strinivasen Naidoo

  2. School of Clinical Medicine Research Laboratory, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    Nathlee Abbai

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  1. Meleshni Naicker
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Naicker, M., Abbai, N. & Naidoo, S. Bipolar limbic expression of auto-immune thyroid targets: thyroglobulin and thyroid-stimulating hormone receptor. Metab Brain Dis 34, 1281–1298 (2019). https://doi.org/10.1007/s11011-019-00437-w

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