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Title: Signalling in hypothalamic tanycytes
Author: Benford, Heather Elizabeth
ISNI:       0000 0004 5355 8788
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2014
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Hypothalamic tanycytes are a specialised type of glial cell found lining the 3rd ventricle. They possess a cell body that contacts the cerebrospinal fluid (CSF) and a single long process that projects into the hypothalamic parenchyma, some of which are known to extend into the Arcuate nucleus (ARC) and Ventromedial nucleus (VMN), two key hypothalamic regions involved in control of energy homeostasis. Owing to their unique position, it has been hypothesised that hypothalamic tanycytes may be able to detect nutrient related signals in the CSF and influence the neurons of the ARC and VMN leading to changes in food intake and body weight. Tanycytes have recently been shown to be glucosensitive, responding to brief application of glucose by generating Ca2+ waves. However the signalling pathways inducing this response remain elusive. Here we investigated the nature of tanycyte glucosensing. Using Ca2+ imaging techniques we show that tanycytes can respond to glucose and non-nutritive sweeteners implicating the sweet taste receptor as the mediator of tanycyte glucosensitivity. We further show that activation of the sweet taste receptor induces release of ATP from tanycytes via pannexin hemichannels allowing propagation of the Ca2+wave. In addition we also investigated whether hypothalamic tanycytes can communicate to secondary cells within the hypothalamus. Using multiphoton stimulation of a single tanycyte, we show that Ca2+ waves can be generated, which spread between neighbouring cells as well as along the tanycyte process towards the hypothalamic parenchyma. We also demonstrate signalling in secondary cells following tanycyte stimulation is likely the result of tanycyte communication. Thus hypothalamic tanycytes are able to detect sweet tasting compounds in the CSF via the sweet taste receptor, this induces Ca2+ signalling which may be communicated to secondary cells, including the neurons of the ARC and VMN, where it may be integrated to induce changes in energy homeostasis.
Supervisor: Not available Sponsor: Medical Research Council (Great Britain)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology