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Auswirkung einer selektiven p75-Neurotrophinrezeptor-Defizienz im Immun- oder Zentralnervensystem auf die experimentelle autoimmune Enzephalomyelitis

dc.contributor.advisorStadelmann-Nessler, Christine Prof. Dr.
dc.contributor.authorKrug, Marlon
dc.titleAuswirkung einer selektiven p75-Neurotrophinrezeptor-Defizienz im Immun- oder Zentralnervensystem auf die experimentelle autoimmune Enzephalomyelitisde
dc.title.translatedEffects of a selective deficiency of the p75 neurotrophin receptor in the immune system or central nervous system on the experimental autoimmune encephalomyelitisde
dc.contributor.refereeStadelmann-Nessler, Christine Prof. Dr.
dc.description.abstractengThe clinical manifestation of multiple sclerosis (MS) is largely due to axonal damage and axonal loss caused by inflammation and demyelination. As an explanation for the different extents of axonal damage and thus the clinical differences of impairment between patients, polymorphisms in neurotrophin signaling pathways, among other things, are discussed. In the last decades experimental autoimmune encephalomyelitis (EAE) has been established as a model to study the pathogenesis of MS. In 2004 Copray et al. showed that deficiency of the p75 neurotrophin receptor (p75NTR) results in a more severe disease course after the induction of EAE in mice. He postulated a stabilizing effect of p75NTR on the integrity of the blood-brain barrier (BBB). P75NTR however, is not only expressed on endothelial cells, but also on cells of the central nervous system and the immune system. In this study I examined whether and how a selective deficiency of p75NTR in the CNS and the immune system affects EAE. Therefore, we created bone marrow chimeras using p75NTR knockout mice in which either only the cells of the immune system or the CNS had a functioning p75NTR. The acute and chronic phase of active EAE and the acute phase of “passive” EAE induced by adoptive transfer of activated T cells were examined. A histological evaluation of the mice in terms of quality and quantity of inflammation, demyelination and axonal damage or loss was made. Regarding the clinical symptoms, a not more severe disease course was observed in the p75NTR deficient animals. In the late chronic phase of active EAE, mice deficient of p75NTR in the CNS showed a significantly milder disease course. In the experiments on acute EAE induced by adoptive transfer, I found an increased axonal damage in the animals with p75NTR deficient CNS. These results support the hypothesis that p75NTR plays an axono-protective role in CNS inflammation. As a possible explanation, one could adduce the HIF-1α pathway, whose expression, among other things, is dependent on p75NTR and in the case of p75NTR deficiency, cannot perform its cell protective function sufficiently. Furthermore I draw the conclusion that due to the same extent of inflammation in all experimental groups, the integrity of the BBB is only marginally influenced by p75NTR deficiency. Also, my results speak against a substantial influence of p75NTR on the maturation, activation and proliferation of T
dc.contributor.coRefereeLiebetanz, David Prof. Dr.
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullMedizin (PPN619874732)de

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