Dhillon, Karendeep (2021) On the roles of hypothalamic tanycytes in energy homeostasis. PhD thesis, University of Warwick.

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Abstract

The hypothalamus is a key player in energy homeostasis. While hypothalamic neurons have been heavily focused on, tanycytes, glial cells that line the wall of the 3rd ventricle (3V) have gained recent attention. Tanycytes are privileged in their access to hypothalamic nuclei, circulating factors within the blood and cerebrospinal fluid. With knowledge of their ability to respond to nutrients in vitro, this work aimed to elucidate their functions in vivo.

The role of tanycytes was scrutinized using WT and mutant mice lacking the Tas1r1 taste receptor (KO). This mutation increases tanycyte sensitivity to L-arginine (Arg) in male mice and decreases sensitivity in female mice. In response to Arg gavage, all groups except KO female mice exhibited reduced locomotor activity, linking tanycyte responses to physical activity for the first time.

Glucose biosensors were implanted into the 3V and Arcuate nucleus (Arc) of mice to develop our understanding of nutrient access to these areas. Intraperitoneal injection, food intake and consumption of a glucose solution all rapidly increased glucose concentration within the 3V, while the concentration within the Arc remained stable. The observed glucose dynamics resembled the environment required to elicit strong Ca2+ responses in tanycytes.

Miniature microscopes were used to visualise tanycyte signalling within awake, behaving mice for the first time. This thesis documents responses to glucose, amino acids and food intake. While further characterisation is required, tanycytes are shown to respond to low levels of glucose within 10 minutes.

This thesis presents the novel findings that tanycytes may have influence over energy expenditure, respond to nutrients in vivo, and that glucose rapidly increases within the 3V but not the Arc. It strongly suggests that previous in vitro work is physiologically relevant and further solidifies the role of tanycytes in nutrient detection since they are unlikely to access the Arc directly. 1

Item Type:	Thesis (PhD)
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General)
Library of Congress Subject Headings (LCSH):	Hypothalamus, Homeostasis, Neuroglia, Biosensors, Blood glucose, Ingestion
Official Date:	June 2021
Dates:	Date Event June 2021 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Dale, Nicholas ; Bretschneider, Till
Format of File:	pdf
Extent:	217 leaves : illustrations
Language:	eng

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