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The WATCH project: Tanycytes in health and disease
In our aging societies, maintaining health and limiting age-related metabolic or cognitive disorders are of primordial importance not only for the well-being of the individual but also from the economic and societal points of view. The Synergy project Well-Aging and the Tanycytic Control of Health (WATCH), funded by the European Research Council (ERC), is a high-impact project conducted by Vincent Prévot, a neuroendocrinologist working for the French national health research institute (Inserm), in Lille, France; Markus Schwaninger, a neurologist at the University of Lübeck, Germany; and Ruben Nogueiras, an expert in molecular metabolism at the University of Santiago de Compostela in Spain. Together, these three teams aim to understand how a small and highly specialized population of brain cells called tanycytes regulate a variety of physiological processes, and the implications of their function or dysfunction for healthy aging.

Brain infection by SARS-CoV-2: Lifelong consequences
The WATCH team, founded to elucidate the role played by specialized brain cells called tanycytes in various physiological processes, has been investigating how and where the SARS-CoV-2 virus infects the brain, and some long-term consequences of this neuro-invasion. The European Research Council (ERC) Synergy project WATCH (Well-Aging and the Tanycytic Control of Health) brings together the teams of three principal investigators: Vincent Prevot, a neuroendocrinologist working for the French National Health Research Institute (INSERM) in Lille, France; Markus Schwaninger, a neurologist at the University of Lübeck, Germany; and Ruben Nogueiras, an expert in molecular metabolism at the University of Santiago de Compostela in Spain. Together, they are researching how tanycytes – highly specialized cells residing in a tiny part of the brain called the hypothalamus – regulate various physiological processes.

Yes ; Long-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12h:12h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling. ; BBSRC (grant number BB/K001043/1) and the Scottish Government.

Bridging brain barriers for gene therapy
Reflecting on the challenges in treating brain diseases, this article explores ways to transduce the blood-brain barrier as well as the critical role of tanycytes as a target for gene therapy vectors. It is vital that the precious central nervous system is protected from exogenous harmful factors that can damage it. As an innate helmet, the skull protects the brain from mechanical trauma. The blood-brain barrier, on the other hand, serves as a much less conspicuous shield that prevents molecular injury from taking place.

We thank Donna Wallace and the animal house staff for their help with the animal studies. We thank Pat Bain for help in preparing the figures. This work was supported by the Biotechnology and Biological Science Research Council (BBSRC) grant number BB/K001043/1 (G.H., A.W.R., P.N.S., P.J.Mc. and P.J.M.) and the Scottish Government (A.W.R., L.M.T., C.D.M. and P.J.M.). ; Peer reviewed ; Publisher PDF