Die Bedeutung des p75-Neurotrophinrezeptors während der De- und Remyelinisierung im Cuprizon- Modell der Multiplen Sklerose

The significance of the p75NTR during de- and remyelination in cuprizone-induced demyelination of Multiple Sclerosis

by Susann-Cathrin Schüle
Doctoral thesis
Date of Examination:2013-06-11
Date of issue:2013-05-30
Advisor:Prof. Dr. Christine Stadelmann-Nessler
Referee:Prof. Dr. Inga Zerr
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-3851

 

 

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Abstract

English

Multiple sclerosis (MS), the most frequent central nervous system (CNS) autoimmune disease is characterized by multiple focal demyelinated lesions. Partial remyelination of these lesions is frequently observed and considered to be one of the factors contributing to the remission of symptoms.  Neurotrophins are cytokines, which occur not only in the CNS and in the peripheral nervous system (PNS) but also in the immune system. Their effects are mediated through two different kinds of receptors, the tropomyosin- related kinase receptor (trk) and the p75 neurotrophin receptor (p75NTR), which can trigger different or even opposing effects. They can either promote apoptosis and pro-inflammatory pathways or support axonal regeneration. With regard to remyelination, it is well known that p75NTR is able to foster regenerative procedures in the PNS, whereas its role in the CNS has still to be clarified.  This thesis examines the effects of p75NTR deficiency focussing on the extent of de- and remyelination, axonal damage and immigration of CD3+-T-cells into the CNS. To induce cerebral demyelination in wildtype- and p75NTR -deficient mice, the animals were exposed to cuprizone diet. The extent of remyelination was evaluated after stopping the cuprizone diet.  At the time point of demyelination, no differences between wildtype- and p75NTR deficient mice were found regarding the extent of demyelination, axonal damage and number of infiltrating CD3+-T-cells. However, studying the time point of remyelination, the amount of axonal damage was significantly higher and also a tendency towards reduced remyelination and elevated number of immigrated CD3+-T-cells was observed in the absence of p75NTR expression. Thus, this work suggests that the expression of p75NTR might be helpful for regeneration not only the in the PNS but also in the CNS.
Keywords: p75NTR; Multiple Sclerosis; Remyelination
Schlagwörter: p75-Neurotrophinrezeptor; Remyelinisierung im Cuprizon- Modell
 
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