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PhD SP13

Altered cell-cell interaction in experimental diabetic neuropathy – translation of mouse to human

Supervisor (Heidelberg): Peter Nawroth
Co-Supervisor (Groningen): Stephan Bakker
Graduate: Maxime Le Marois

Project description

Several studies which have investigated the underlying pathophysiological mechanisms of diabetic neuropathy (DN) have relied on experiential models, in particularly the treatment with streptozotocin (STZ). However, recent data suggest that STZ has neurotoxic effect [1-3]. It is therefore imperative to translate concepts observed in STZ diabetes to the human situation. To do this, we have established a biobank of peripheral nerves from individuals with and without diabetes, who had undergone amputation. Using this biobank, we can address the following aims: (i) To characterize the activation status and origin of the infiltrating cells in the different compartments of the peripheral nerve; (ii) Since our previous data in the STZ model indicated that the loss of opioid receptors, as well as the opioid itself within the sciatic nerve is a mechanism for the lack of opioid effectiveness in diabetes, we shall study opioid receptor expression and opioid in the biobank available, and  (iii) To establish whether changes in the defense mechanisms against reactive metabolites underlie the structural changes observed in patients with DN.


  1. Bishno, M. et al. Mol Pain.2011 7: 52.
  2. Pabbidi, R.M. et al.  Mol Pain. 2008 4: 9.
  3. Pabbidi, R.M. et al. Mol Pharmacol 2008 73: 995–1004.
  4. Machelska H et al. J Neurosci. 2002; 22: 5588-5596
  5. Mousa SA et al. Brain Behav Immun. 2010; 24:1310-23
  6. Bierhaus, A. et al. Nature Medicine. 2012; 18(6):926-33
  7. Testa, R. et al Diabetes Care. 2007; 30(11):2974-5.
  8. Erusalimsky, J.D. et al. Exp Physiol. 2009;94(3):299-304.
  9. Palmer, A.K. et al. Diabetes. 2015;64(7):2289-98.

Methods used

Proteomics, ultrastructural analysis (immunohistochemistry & electron microscopy), Schwann cell isolation, flow cytometry

Collaboration Partners

  • Martin Schmelz, Mannheim
  • Benito Yard, Mannheim
  • Thomas Fleming, Heidelberg
  • Jens Kroll, Mannheim