Neuropathie

Image description: Intraepidermal nerve fiber in hind foot skin preparations in diabetic and control rats. Representative sections showing immunoreactivity (green) of PGF9.5 positive fibers (arrows) nuclei are counterstained with DAPI (blue).​

Peripheral neuropathy is a serious complication observed in obesity and type 2 diabetes mellitus (T2D). The pathophysiology of this obesity- and diabetes-associated neurological disorder (PDN) includes metabolic, vascular and inflammatory mechanisms but a unifying hypothesis of the culprit pathogenic factors is a matter of debate. Till now, there is no casual therapy against PDN. The present project is based on previous investigations and preliminary studies which have shown enhanced inflammation as well as electrophysiological and morphological changes in peripheral nerves of animals with obesity and/or type 2 diabetes mellitus. Recently, we have shown a correlation between degree of this disorders and dietary iron concentrations. In contrast to previous hypotheses suggesting that iron excess might be the most critical pathogenic cofactor, we found a functionally relevant, increase in distal peripheral nerve pathology with chronic iron depletion rather than iron overload which had little effects. This project focuses on the identification of the role of iron and nerve inflammation in development of PDN in animal models of obesity and metabolic syndrome (ob/ob mice) as well as obesity and T2D (db/db mice). The identification of metabolic and inflammatory mechanisms of PDN should lead to new therapeutic strategies.​​

Baum P, Kosacka J, Estrela-Lopis I, Woidt K, Serke H, Paeschke S, Stockinger M, Klöting N, Blüher M, Dorn M, Classen J, Thiery J, Bechmann I, Toyka KV, Nowicki M (2016) The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN). Metabolism 65(4):391-405.​

Kosacka J, Woidt K, Toyka KV, Paeschke S, Kloeting N, Bechmann I, Blueher M, Thiery J, Ossmann S, Baum P, Nowicki M (2019) The role of dietary non-heme iron load and peripheral nerve inflammation in the development of peripheral neuropathy (PN) in obese non-diabetic leptin-deficient ob/ob mice. Neurol Res. Jan 13:1-13. doi: 10.1080/01616412.2018.1564191;

Paeschke S, Baum P, Toyka KV, Blueher M, Koj S, Kloeting N, Bechmann I, Thiery J, Kosacka J, Nowicki M (2019) The role of Iron and Nerve Inflammation in Diabetes Mellitus Type 2-Induced Peripheral Neuropathy. Neuroscience 406, 496–509.