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Project properties |
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| Title | Neurotransmitter analysis in brain: link with nutritional aspects and ageing |
| Group | Human Nutrition and Health |
| Project type | thesis |
| Credits | 36 |
| Supervisor(s) | Yannick Vermeiren & Marlies Diepeveen-de Bruin |
| Examiner(s) | Renger Witkamp |
| Contact info | yannick.vermeiren@wur.nl |
| Begin date | 2024/02/01 |
| End date | 2024/08/01 |
| Description | Catecholamine (dopamine, (nor)adrenalin) and indolamine (serotonin) neurotransmitters are pivotal in all aspects of human behavior and cognition, with essential roles both in the central and peripheral nervous system. Serotonin has previously been linked with aggression and memory impairment in Alzheimer’s disease, as well as with depression and mood disorders (anxiety) in general, whereas noradrenalin and dopamine have been intrinsically correlated with disease progression and diagnosis in Parkinson’s disease. Apart from their role in (un)healthy cognitive ageing and behavior, these biogenic amines are an important part of gut-brain signaling too. You can think of the microbiota-gut-brain axis. For instance, 90% of the body’s total amount of serotonin is produced within gut, and recent studies have pointed to an important functional role of this indolamine in terms of immune homeostasis and maintenance of optimal brain health, linked with dietary fiber intake. Overall, the synthesis and relative abundancy of brain neurotransmitters heavily relies on the bioavailability of their essential amino acid precursors (tyrosine/phenylalanine, tryptophan), derived from diet. Various detection methods exist, such as high-performance liquid chromatography (HPLC) with electrochemical detection, liquid chromatography coupled to tandem mass spectrometric detection (LC-MS/MS), and, HPLC coupled to fluorescence detection. LC-MS/MS has the highest sensitivity, and is the preferred method of choice. It is, therefore, of the utmost relevance to have laboratory research methods that can quantify various neurotransmitters and their metabolites, so these methods can be applied for the study of nutritional aspects during ageing as mentioned above. Such methods are typically not commercially available, but are developed in the lab. The Nutritional Biomarker Laboratory of the Division of Human Nutrition and Health develops and applies such analytical research methods. We are looking for enthusiastic students who would like to work with advanced equipment in the lab and develop new analytical tools that will help nutrition science.
In this thesis, you will further develop a laboratory method for the quantification of neurotransmitters and metabolites, such as catecholamines (dopamine, (nor)adrenalin; DOPAC, HVA, MHPG) and/or indolamines (serotonin; 5-HIAA; tryptophan). This will involve a literature study, setting up experiments, and optimizing sample extraction and analysis. This method already has been partially explored in the past, but is not yet fully optimized. In the end, we will run a set of samples derived from ongoing studies, to demonstrate in-house applicability and clinical validity of the LC-MS/MS system in nutrition and ageing research. Most likely, the thesis will make use of (i) frozen brains from mice that were part of a study on fiber intake and gut health (gut-brain axis), or, (ii) pig brains that have been studied in relationship to diet and health status. |
| Used skills | Optimizing an LC-MS/MS method for neurotransmitter analysis in brain samples; executing and comparing various sample preparation protocols; exploring clinical adaptations of method development; performing neurotransmitter analyses of frozen animal brain samples; exploring how neurotransmitter alterations may be linked with nutritional aspects in ageing; preparing mobile phases; handling biological specimens; device knowledge and technical aspects of liquid chromatography-mass spectrometry. |
| Requirements | Master Nutrition and Health, specialization B (but lab-skilled), C or F. Or MSc students from other life science programs with affinity for biochemistry and laboratory work, such as Plant Sciences, Biotechnology, Biology, or Molecular Life Sciences, with a keen interest in neurosciences, neurochemistry, ageing, and, nutrition.
-Biochemistry -Neurochemistry -Analytical lab skills -Keen interest in neurosciences, ageing, nutrition |