Metabolic Signaling in the Cerebrospinal Fluid

Abstract

Title: Metabolic Signaling in the Cerebrospinal Fluid Edwin Gidestrand, Degree Project, Programme in Medicine, 2017, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden Supervisor: John-Olov Jansson Introduction: Obesity is a dangerous disease that affects more than 600 million individuals. One rather effective group of drugs used to treat obesity are analogues to the hormone glucagon-like peptide-1 (GLP-1), believed to prevent obesity acting in the brain. Another hormone, leptin, was a promising candidate for treatment of obesity but failed due to leptin resistance in obese individuals. Interleukin-6 is a protein most known for its role in the immune system; however, it can also act as a neuropeptide that decreases appetite. Aim: The overall aim of the study was to further elucidate how the anorectic peptides interleukin-6, GLP-1 and leptin signal via the cerebrospinal fluid (CSF). Method: We used ELISA to measure GLP-1 in human CSF. We continued by administrating leptin to mice lacking the receptor to interleukin-6 on the inside of the ventricles. Finally we used immunohistochemistry to evaluate activation of different brain areas in mice after administration of GLP-1, leptin or interleukin-6. Results: Here we show that human CSF does not contain measurable levels of GLP-1. We further show that the effects of leptin is not influenced by knock-down of the receptor to interleukin-6 on the inside of the ventricles. Finally we show that GLP-1, leptin and interleukin-6 has the potential to activate cells found on the inside of the ventricles. We used immunohistochemistry to identify these cells lining the ventricles as tanycytes. Conclusions: Collectively these findings suggest that at least pharmacologically, glucagon-like peptide-1, leptin and interleukin-6 may exert their effects via the CSF. This may be done by activating special ependymal cells lining the inner surface of the ventricles known as tanycytes.