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The role of tight junction proteins in the pathophysiology of diabetic neuropathy
Germany (bvmd) - Julius-Maximilians Universitaet, Wuerzburg
Anaesthesiology and Critical Care, University of 10 Würzburg, Oberduerrbacher Strasse 6, D-97080 Würzburg, Germany,
Prof. Dr. med. Dr. h.c. N. Roewer
Dr. Reine-Solange Sauer, Prof. Dr. med. Heike Rittner
Type of Research Project
- Basic science
What is the background of the project?
Poor control of blood glucose is an important risk factor for the development of diabetic neuropathy, a complication of diabetes. Diabetic peripheral neuropathy is associated with considerable mortality, morbidity, and diminished quality of life. Its development is multifactorial and the exact pathological mechanisms involved are not completely understood. Several earlier studies point towards in blood nerve barrier dysfunction in diabetic neuropathy. Hyperglycemia results in elevated intracellular glucose in peripheral nerves, leading to intracellular hyperosmolarity and efflux of osmolytes. The consequence would be the alteration of tight junction proteins and structural breakdown of the perineurial barrier around sensory nerves and nociceptors. There is increasing evidence that decreased tight junction proteins like claudin-1 or ZO-1 are the major cause of blood nerve barrier breakdown and increased permeability linked with several of neurodegenerative diseases and traumatic or inflammatory neuropathy. We hypothesize that hyperglycemia in diabetic rats leads to time-dependent tight junction protein alterations and increased permeability of blood nerve barrier that contribute to neuronal damage.
What is the aim of the project?
The aim of the project is to identify tight junction proteins that are changed in mRNA expression levels in the sciatic nerve during diabetic conditions and the possible mechanisms of hyperglycemia induced tight junction proteins (TJP) alteration and blood nerve barrier breakdown.
What techniques and methods are used?
Quantitative Real time polymerase chain reaction (RT PCR), Western Blot and immunostaining will be performed to assess TJP expression at micro RNA and protein levels. Evans blue albumin will be used as a fluorescent tracer to demonstrate the increased permeability of the blood nerve barrier in the sciatic nerve of the Streptozotocin-induced diabetic rat.
What is the role of the student?
What are the tasks expected to be accomplished by the student?
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Knowledge of techniques is an advantage but not prerequisites
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system
- Ann N Y Acad Sci. 2017 Jul 28. doi: 10.1111/nyas.13436. [Epub ahead of print] Sauer RS1; Kirchner J1; Yang S1;2; Hu L1;2; Leinders M3; Sommer C3; Brack A1; Rittner HL1.
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