Thyroid Hormone and the Neuroglia: Both Source and Target

Abstract

Thyroid hormone plays a crucial role in the development and function of the nervous system. In order to bind to its nuclear receptor and regulate gene transcription thyroxine needs to be activated in the brain. This activation occurs via conversion of thyroxine to T3, which is catalyzed by the type 2 iodothyronine deiodinase (D2) in glial cells, in astrocytes, and tanycytes in the mediobasal hypothalamus. We discuss how thyroid hormone affects glial cell function followed by an overview on the fine-tuned regulation of T3 generation by D2 in different glial subtypes. Recent evidence on the direct paracrine impact of glial D2 on neuronal gene expression underlines the importance of glial-neuronal interaction in thyroid hormone regulation as a major regulatory pathway in the brain in health and disease.

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

“…T 3 can also enhance neuronal differentiation induced by retinoic acid treatment of embryonic stem cells (525). Glial cells are also responsive to T 3 (526). For example, the activity of the cell maturation marker glutamine synthetase increases in cultured cerebellar astrocytes in response to T 3 (527).…”

“…For example, the activity of the cell maturation marker glutamine synthetase increases in cultured cerebellar astrocytes in response to T 3 (527). Notably, thyroid hormone-evoked changes in neuronal function often involve glia-mediated actions (526). For example, thyroid hormone up-regulates voltage-activated sodium current in cultured postnatal hippocampal neurons through T 3 -dependent secretion of basic fibroblast growth factor from hippocampal astrocytes (528).…”

Neuronal Hypoxia Induces Hsp40-Mediated Nuclear Import of Type 3 Deiodinase As an Adaptive Mechanism to Reduce Cellular Metabolism

“…In contrast, the type 3 deiodinase (D3) pathway is thought to inactivate T3 intracellularly, and this depletion of T3 terminates thyroid hormone-driven metabolic events (Freitas et al, 2010). These deiodinase-mediated control pathways for thyroid hormone action are active in the brain, with the glial D2 generating most T3 in the CNS and the neuronal D3 inactivating both T4 and T3 Mohácsik et al, 2011).…”

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

“…In recent years attention has been paid to the effect of thyroid hormones on the properties and activity of microglial cells [8][9][10]. These cells significantly affect defensive functions in the brain, but in the specific microenvironment formed by gliomas and particularly glioblastoma multiforme (GBM) their defensive properties can change and microglia begin to intensify and deepen the neoplastic process [10,11].…”