Role of maternal thyroid hormones in the developing neocortex and during human evolution

Abstract

The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review

“…In turn, the aforementioned adverse events during pregnancy can disrupt the function of the developing nervous system resulting in poor offspring neurodevelopment (9). Both animal and human studies have established that important phases of neocortex development can be altered by early maternal thyroid dysfunction and result in persistent negative consequences in offspring (10,11,12,13). One of the mechanism by which thyroid hormones may influence brain development is via the regulation of the expression of brain-derived neurotrophic factor and Reln gen; Reln produces Reeln, essential for the proper migration and the establishment of neocortical layers (14).…”

Thyroid hormones in fetal growth and prepartum maturation

“…This review examines the developmental control of fetal T 4 and T 3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on the maturation of somatic tissues essential for survival immediately at birth. The important role of thyroid hormones in brain development is not considered here as this has been reviewed extensively in recent years (Horn & Heuer 2010, Patel et al 2011, Puig-Domingo & Vila 2013, Stenzel & Huttner 2013). …”

Cognitive Enhancement

“…The thyroid gland is a butterfly-shaped organ that develops within the anterior side of the neck, with physical attachment to underlying tracheal cartilage. It responds to pituitary secretion of thyroid-stimulating hormone (TSH) by augmenting the synthesis and release of two chemicals, thyroxine (T 4 ) and triiodothyronine (T 3 ), which go on to regulate anabolic energy metabolism and hormone sensitivity throughout the body (Stenzel and Huttner 2013). The brain is one of the primary sites of action for T 4 /T 3 during development and adulthood (Kester et al 2004).…”