VITD-COGN / ANALYSIS OF VITAMIN D METABOLITES IN BRAIN TISSUE AND CEREBROSPINAL FLUID OF RATS AND THE RELATIONSHIP BETWEEN VITAMIN D LEVELS AND COGNITIVE FUNCTION, Director proiect: Gall Zsolt
| Proposal Registration Code | PN-III-P1-1.1-PD-2019-0507 |
| Project Registration Code | PD 102/2020 |
| Project Acronym | VITD-COGN / Analysis of vitamin D metabolites in brain tissue and cerebrospinal fluid of rats and the relationship between vitamin D levels and cognitive function |
| Purpose and project planning | Understanding the role of vitamin D in the brain cannot be complete without proper knowledge regarding its concentrations at neuronal level in behaving animals. Different approaches (e.g. intracerebral injections, microdialysis) were adopted to increase vitamin D levels in the brain in order to study its effects in discrete regions and to correlate them with disorders. The main objective of this project is to develop and validate analytical methods to determine the concentration of vitamin D3 metabolites in microdialysate and brain homogenate, and to correlate them with serum levels. The second aim is to study the influence of vitamin D supplementation on the cognitive function in vitamin D deficient rats, and to quantify vitamin D metabolites in the brain after chronic treatment with vitamin D. |
| Project Start Date | 01.09.2020 |
| Project End Date | 01.09.2022 |
| Project Duration | 24 months |
| Total budget value | 246.550,00 lei |
| Funding | Ministry of Research and Innovation, CNCS-UEFISCDI |
| Main objectives | Aims: – to study of the pharmacokinetics of vitamin D3 and its metabolites (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) – to evaluate the correlation between serum 25-hydroxyvitamin D and brain exposure – to investigate the correlation between the status of vitamin D3 and cognitive function in rats Work plan. The development of analytical methods for the quantification of vitamin D metabolites (vitamin D3, 25-OH-D3, 1α,25-(OH)2-D3) will be the first and the most important task. For establishing the concentration range of each analyte it is necessary to determine the analyte recovery after a preliminary in vitro testing of the microdialysis probes, and to measure the basal level of the analytes of interest in brain homogenate. The specificity, linearity, precision and accuracy of the newly developed method will be investigated. This phase will take 6 months presumably. Another approximately 6 month will be dedicated for the fine tuning of the analytical method and sampling method, and, if necessary, for the implementation of specific sample preparation technique. The next step will be correlation of the concentration of vitamin D metabolites with the cognitive performance of rats using ethopharmacological tests. Three group of rats will be used to measure the extracellular levels of vitamin D and its metabolites during/after the testing period. Vitamin D deficiency will be induced by nutritional restrictions. The animals will be fed with controlled amount of vitamin D. In this way, the relationship between vitamin D level and specific behavioral manifestation (i.e. learning and memory) can be studied. For this phase an additional 12 months are required. |
| Team: | Name -> Role Gáll Zsolt -> Leader Imre Silvia -> Mentor |
| Results | The results of the current project would contribute to the understanding of vitamin D actions in the brain by providing a detailed insight into the local synthesis and metabolism of vitamin D metabolites. The proposed methodology would be complementary to the currently used approaches (e.g. intracerebral injections of vitamin D metabolites) by evaluating the vitamin D status of the brain after peripheral administration and addressing the question of whether vitamin D supplementation could have beneficial role in dementia or other psychiatric disorders. |
| Host institution | George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures |