The Thyroid Hormone Receptor α1 Protein Is Expressed in Embryonic Postmitotic Neurons and Persists in Most Adult Neurons

Abstract

Thyroid hormone is essential for brain development where it acts mainly through the thyroid hormone receptor α1 (TRα1) isoform. However, the potential for the hormone to act in adult neurons has remained undefined due to difficulties in reliably determining the expression pattern of TR proteins in vivo. We therefore created a mouse strain that expresses TRα1 and green fluorescent protein as a chimeric protein from the Thra locus, allowing examination of TRα1 expression during fetal and postnatal development and in the adult. Furthermore, the use of antibodies against other markers enabled identification of TRα1 expression in subtypes of neurons and during specific stages of their maturation. TRα1 expression was first detected in postmitotic cells of the cortical plate in the embryonic telencephalon and preceded the expression of the mature neuronal protein NeuN. In the cerebellum, TRα1 expression was absent in proliferating cells of the external granular layer, but switched on as the cells migrated towards the internal granular layer. In addition, TRα1 was expressed transiently in developing Purkinje cells, but not in mature cells. Glial expression was found in tanycytes in the hypothalamus and in the cerebellum. In the adult brain, TRα1 expression was detected in essentially all neurons. Our data demonstrate that thyroid hormone, unexpectedly, has the capacity to play an important role in virtually all developing and adult neurons. Because the role of TRα1 in most neuronal cell types in vivo is largely unknown, our findings suggest that novel functions for thyroid hormone remain to be identified in the brain.

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…The fused tag allows detection of TR isoform expression by immunohistochemistry (IHC) or immunofluorescence in tissue sections or whole-mount preparations and offers the possibility of detection at single cell resolution. Thra1 gfp mice carry green fluorescent protein (GFP) fused in-frame at the C-terminus of the intact TRa1 protein (469). Detection of TRa1-GFP protein has been reported in specific brain tissues and cell types.…”

Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells

“…When grafted in vivo, or when deprived of serum, they stop proliferating and differentiate into neuron-like cells within 1 wk. C17.2 cells probably originate from the cerebellum external granular layer, a transient structure populated by granular neuron precursors, and like these natural progenitors, express few if any TRs (30)(31)(32). We transfected these cells to express in a stable manner either TRα1 or TRβ1 and the reporter enhanced green fluorescent protein (Fig.…”

Hormony tarczycy w ośrodkowym układzie nerwowym (OUN) i ich wpływ na nowotworzenie, zwłaszcza na rozwój i przebieg glioblastoma multiforme — hipoteza badawcza

“…Nuclear receptors of thyroid hormones THRA1, THRB1, and the isoforms of these receptors are present in brain cells in humans from the 8th-10th weeks of foetal life [43,44]. During this period, the presence of THRA1 prevails, particularly in the external part of the cerebral cortex and in the hypothalamus [43,44].…”

“…During this period, the presence of THRA1 prevails, particularly in the external part of the cerebral cortex and in the hypothalamus [43,44]. From about the 15 th week of foetal life also THRB1 and THRB2 are detected in the developing brain.…”

“…Receptory jądrowe hormonów tarczycy THRA1, THRB1 i izoformy tych receptorów są obecne w komórkach mózgu człowieka począwszy od 8.-10. tygodnia życia płodowego [43,44]. W tym okresie przeważa obecność THRA1, zwłaszcza w zewnętrznej części kory i w podwzgórzu [43,44].…”