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Search for new therapeutic targets and/or potential biomarkers for diabetic neuropathyew Project
Denmark (IMCC) - Aarhus university, Aarhus
Department of Biomedicine, Aarhus University, Høegh-Guldbergagade 10, building 1116, 8000 Aarhus C, Denmark
Nádia Pereira Gonçalves
Type of Research Project
- Basic science
What is the background of the project?
The most common complication of diabetes is peripheral neuropathy, which has a prevalence as high as 50% and is characterized by damage to neurons, Schwann cells and blood vessels within the nerve. The pathogenic mechanisms of diabetic neuropathy remain poorly understood, impeding the development of targeted therapies to treat nerve degeneration and its most disruptive consequences of sensory loss and neuropathic pain. Involvement of Schwann cells has long been proposed, and new research techniques are beginning to unravel a complex interplay between these cells, axons and microvessels that is compromised during the development of diabetic neuropathy. Therefore, further studies are necessary in order to understand the integral factors for the pathogenesis of diabetic neuropathy, and how disruption of the interactions between Schwann cells, axons and microvessels contribute to the disease progression.
What is the aim of the project?
The main goal of this research project is to validate candidate targets and find potential biomarkers for type 2 diabetic neuropathy.
What techniques and methods are used?
This project is based on results obtained with RNA sequencing analysis, where several genes were found up or downregulated in the sciatic nerves of a mouse model with peripheral neuropathy, secondary to type 2 diabetes. Neuron and Schwann cell primary cultures will be performed and stimulated with high glucose or lipids to mimic diabetic neuropathy. Candidate target expression, both at gene and protein levels, will be analyzed by western blotting, real-time polymerase chain reaction (qPCR) and immunocytochemistry using confocal microscopy. Sciatic nerves or dorsal root ganglia from diabetic mice will be cryosectioned for further analysis by immunohistochemistry.
What is the role of the student?
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Working under supervision, the student will perform necessary manipulations on primary cell cultures. These include: • Cell purification; • Change the cell media; • Expansion of Schwann cells; • Cell stimulation with glucose or lipids; • Collection of cells for analysis. Regarding mouse tissues, the student is expected to follow and help with: • Immunohistochemistry; • Colocalization studies with confocal microscopy.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes. The student will be provided with some review articles to better understand the field with what she/he will be working on. Participation in the lab journal clubs and background to the experiments.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Familiarity with the provided literature. Working in a class I laboratory.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Students in biomedical fields
- Schwann cell interactions with axons and microvessels in diabetic neuropathy. Gonçalves NP; Vægter CB; Andersen H; Østergaard L; Calcutt NA; Jensen TS. Nat Rev Neurol. 2017 Mar;13(3):135-147. doi: 10.1038/nrneurol.2016.201
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