Thyroid hormone, gene expression, and Central Nervous System: Where we are

Author(s)

Giannocco, Gisele ^{[1, 2]} ; Letro Kizys, Marina Malta ^[1] ; Maciel, Rui Monteiro ^[1] ; de Souza, Janaina Sena ^{[3, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP EPM, Dept Med, Lab Endocrinol & Med Translat, Rua Pedro de Toledo 669, 11 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP, Dept Ciencias Biol, BR-09920000 Diadema, SP - Brazil

^[3] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 - USA

• Document type: Review article
• Source: SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY; v. 114, n. SI, p. 47-56, JUN 2021.
• Web of Science Citations: 1

Abstract

Thyroid hormones (TH; T3 and T4) play a fundamental role in the fetal stage to the adult phase, controlling gene and protein expression in virtually all tissues. The endocrine and CNS systems have relevant interaction, and the TH are pivotal for the proper functioning of the CNS. A slight failure to regulate TH availability during pregnancy and/or childhood can lead to neurological disorders, for example, autism and cognitive impairment, or depression. In this review, we highlight how TH acts in controlling gene expression, its role in the CNS, and what substances widely found in the environment can cause in this tissue. We highlight the role of Endocrine Disruptors used on an everyday basis in the processing of mRNAs responsible for neurodevelopment. We conclude that TH, more precisely T3, acts mainly throughout its nuclear receptors, that the deficiency of this hormone, either due to the lack of its main substrate iodine, or by to incorrect organification of T4 and T3 in the gland, or by a mutation in transporters, receptors and deiodinases may cause mild (dysregulated mood in adulthood) to severe neurological impairment (Allan-Herndon-Dudley syndrome, presented as early as childhood); T3 is responsible for the expression of numerous CNS genes related to oxygen transport, growth factors, myelination, cell maturation. Substances present in the environment and widely used can interfere with the functioning of the thyroid gland, the action of TH, and the functioning of the CNS. (AU)

• FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
• Grantee: Janaína Sena de Souza
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 17/23169-1 - Thyroid hormones action on 3xTg-AD (APPswe, PS1m146v, tauP301L) Alzheimer Disease´s mice model.
• Grantee: Gisele Giannocco
• Support type: Regular Research Grants
• FAPESP's process: 18/22763-0 - Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells
• Grantee: Janaína Sena de Souza
• Support type: Scholarships abroad - Research Internship - Post-doctor