Unveiling the Importance of Tanycytes in the Control of the Dialogue Between the Brain and the Periphery

Tanycytes, a specialized type of ependymoglial cell, modulate an interesting cycle of communication between the brain and the periphery for energy homeostasis and reproduction. While most circulating factors do not enter the brain because of the blood-brain barrier (BBB), homeostatic signals from the periphery converge on the hypothalamus-a brain region influencing feeding and energy expenditure-through a privileged route that bypasses the brain barrier. Research on the why's and the wherefore's of this peculiar brain-periphery communication has made substantial progress in the recent past. One of the compelling revelations has been the ability of tanycytes to adapt their physiology based on the metabolic status of an individual-a key to understanding how tanycytes regulate the transfer of peripheral metabolic hormones into the brain and communicate reciprocally with brain neuronal networks for the regulation of food intake and energy homeostasis. It has been shown that tanycytes adapt by altering the functional and structural organization of the blood-hypothalamus barrier under different metabolic conditions. Moreover, attempts have been made to decode the plasticity and the diversity of tanycytes by morphological and transcriptomic analyses, primarily at the single-cell level. Tanycytes also possess neural stem cell properties as a result of their putative descent from radial glial cells, and may promote hypothalamic neurogenesis in response to dietary or reproductive signals. Thus, tanycytes form the gatekeepers of metabolic signals connecting the loop of behavior, hormonal changes, signal transduction, and neuronal activation. In this chapter, we assess recent advances in the understanding of tanycytic plasticity and function in the hypothalamus and the associated molecular mechanisms, with special emphasis on the techniques and experimental models implemented to achieve these objectives.