Spatio-temporal effects of iodine/thyroid hormone deficiency on neurodevelopment and plausible amelioration approaches beyond the critical window

Thyroid hormones (TH) are key endocrine players in mammalian brain development. They regulate the cellular and molecular aspects of several dynamic neurodevelopmental processes, including neurogenesis, neuronal migration, astrogliogenesis, synaptogenesis, neuronal apoptosis, and myelination in a very precise spatiotemporal manner. Therefore, TH deficiency during early brain development leads to severe and often irreversible mental disabilities in humans. Additionally, the requirement of TH for the development of different brain areas is also unique. This spatio-temporal dependence of neurodevelopment on maternal and fetal TH availability introduced the concept of a “critical window,” which refers to a time frame during the development of the brain wherein the availability of TH is indispensable. In this review, we cover our recent understanding of the spatio-temporal spectrum of TH-dependent neocortical and cerebellar development, along with the use of omega-3-fatty acids and histone deacetylase inhibitors to mitigate the impact of hypothyroidism on mammalian brain development.