The survival of an organism depends on its being able to maintain energy balance, in other words, to control the brain hormonal systems that receive and understand metabolic and other signals indicating the body’s needs and adapting the organism’s response depending on these needs. Tanycytes are a type of specialized brain cells called glia. They occur in the median eminence of the hypothalamus, a small region at the base of the brain that regulates a very large number of bodily functions through the complex exchange of hormones and other signals between the brain and the peripheral organs. Specifically, tanycytes line the floor of the third ventricle – a liquid-filled pocket inside the brain that communicates with other such pockets, creating a canal system within the brain. Because of their ideal placement, contacting both the blood through porous blood vessels at the base of the median eminence, and the cerebrospinal fluid, the liquid that fills the canals, as well as the position of their “end-feet”, which surround the terminals of neurons that secrete some of the hypothalamic hormones, these very versatile and adaptable cells act as linchpins of various physiological processes. Given the porous nature of the blood vessels underlying the median eminence, tanycytes also act as a barrier protecting the brain, and especially hypothalamic neurons that must respond to various bodily signals including hunger or satiety, from seeing these signals except when the context is right, and in fact, they actively shuttle these signals into the brain from the blood, allowing the right hypothalamic neurons to see and respond to them.
The specific aims of the WATCH project are:
1 – Pinpointing differences in gene expression between tanycytes located at different levels of the ventricular wall and thus identifying them based on the “markers” they express, and understanding how their genetic profile allows them to regulate bodily functions and what happens when they dysfunction.
2 – Identifying new subpopulations of tanycytes and the endothelial cells – cells lining the blood vessels – with which they associate, based on the genes they express, and determining how these characteristics change as a function of the bodily state or under disease conditions.
3 – Confirming the identity of the new sub populations of tanycytes on the basis of their function, and determining how they are regulated at the experimental level.
4 – Understanding whether the tanycytic shuttle that carries signals into the brain breaks down in metabolic diseases or with age, using drugs to reactivate the shuttle, and studying whether this can improve the brain’s response to these signals in obese patients or in patients with age-related impairments of learning and memory.