Thyroid Hormone Regulation of Adult Neurogenesis

Abstract Thyroid hormone is classically known to play a crucial role in neurodevelopment. The potent effects that thyroid hormone exerts on the adult mammalian brain have been uncovered relatively recently, including an important role in the modulation of progenitor development in adult neurogenic niches. This chapter extensively reviews the current understanding of the influence of thyroid hormone on distinct stages of adult progenitor development in the subgranular zone (SGZ) of the hippocampus and subventricular zone (SVZ) that lines the lateral ventricles. We discuss the role of specific thyroid hormone receptor isoforms, in particular TRα1, which modulates cell cycle exit in neural stem cells, progenitor survival, and cell fate choice, with both a discrete and overlapping nature of regulation noted in SGZ and SVZ progenitors. The balance between liganded and unliganded TRα1 can evoke differing consequences for adult progenitor development, and the relevance of this to conditions such as adult-onset hypothyroidism, wherein unliganded thyroid hormone receptors (TRs) dominate, is also a focus of discussion. Although a detailed molecular understanding of the specific thyroid hormone target genes that contribute to the neurogenic actions of thyroid hormone is currently lacking, we highlight the current state of knowledge and discuss avenues for future investigation. The goal of this chapter is to provide a comprehensive and detailed analysis of the effects of thyroid hormone on adult neurogenesis, to discuss putative molecular mechanisms that mediate these effects, and the behavioral, functional, and clinical implications of the neurogenic actions of thyroid hormone.