Abstract
The morphological alterations of cortical lamination observed in mouse models of developmental hypothyroidism prompted the recognition that these experimental changes resembled the brain lesions of children with autism; this led to recent studies showing that maternal thyroid hormone deficiency increases fourfold the risk of autism spectrum disorders (ASD), offering for the first time the possibility of prevention of some forms of ASD. For ethical reasons, the role of thyroid hormones on brain development is currently studied using animal models, usually mice and rats. Although mammals have in common many basic developmental principles regulating brain development, as well as fundamental basic mechanisms that are controlled by similar metabolic pathway activated genes, there are also important differences. For instance, the rodent cerebral cortex is basically a primary cortex, whereas the primary sensory areas in humans account for a very small surface in the cerebral cortex when compared to the associative and frontal areas that are more extensive. Associative and frontal areas in humans are involved in many neurological disorders, including ASD, attention deficit-hyperactive disorder, and dyslexia, among others. Therefore, an evo-devo approach to neocortical evolution among species is fundamental to understand not only the role of thyroid hormones and environmental thyroid disruptors on evolution, development, and organization of the cerebral cortex in mammals but also their role in neurological diseases associated to thyroid dysfunction.
Highlights
Evolutionary developmental biology studies the developmental processes of different organisms to determine the ancestral relationships between them and to discover how developmental processes evolved
A second issue is that several psychiatric diseases, including autism spectrum disorders (ASD), show a wide spectrum of different phenotypes, which are the result of both genetic and environmental factors [4]; including among the latter the interaction of comorbid disorders such as hypothyroidism and hypothyroxinemia [5]
Recent studies have reported that thyroid hormone deficiency might contribute to increase the number of autism phenotypes, and that disorders associated with hypothyroidism and hypothyroxinemia, such as intellectual impairment, seizures, and anxiety, are comorbid of ASD
Summary
Evolutionary developmental biology (evo-devo) studies the developmental processes of different organisms to determine the ancestral relationships between them and to discover how developmental processes evolved. Emx and Fgf genes share reciprocal functions in regulating cortical patterning; in the frontal cortex, this is accomplished at least in part through controlling the levels of Erm, Er81, Pea, and Sp8 expression [118, 119] These results support the protomap model [115, 120, 121] because neurons are committed to their areal position at the time of their last cell division (the asymmetrical one) in the proliferative zones in the absence of thalamic afferent inputs, individual cortical areas may be selectively changed in size during the course of evolution by altered expression signals of their downstream transcription factor signaling mechanisms, as mentioned above [2]. Late maternal hypothyroidism (LMH) during gestation has been used as a model to study the role of maternal thyroid hormones from the onset of fetal thyroid function [169]
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