Die Auswirkung von verschiedenen Proteasom-Inhibitoren auf die Wallersche Degeneration peripherer Nerven in vitro und in vivo

Denninger, Stefan Christoph

dc.contributor.advisor	Siebert, Heike Dr.	de
dc.contributor.author	Denninger, Stefan Christoph	de
dc.date.accessioned	2013-08-06T09:20:08Z	de
dc.date.available	2013-09-11T22:50:04Z
dc.date.issued	2013-08-06	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0001-BAFB-8	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3968
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Die Auswirkung von verschiedenen Proteasom-Inhibitoren auf die Wallersche Degeneration peripherer Nerven in vitro und in vivo	de
dc.type	doctoralThesis	de
dc.title.translated	The effect of different proteasome inhibitors on Wallerian degeneration of peripheral nerves in vivo and in vitro	de
dc.contributor.referee	Brück, Wolfgang Prof. Dr.	de
dc.date.examination	2013-09-04	de
dc.description.abstracteng	The present study examined the effects of proteasome inhibitors on Wallerian degeneration (WD) in the peripheral nervous system on the example of sciatic nerve sectioning in vivo and on the basis of nerve-macrophage co-cultures in vitro. The Wallerian degeneration describes the processes of discontinuity in the nervous system by chemical-toxic, metabolic or mechanical causes. The ubiquitin-proteasome-system (UPS), in addition to the lysosome, provides most of the proteolysis and is one of the main effectors of coordinating all processes running for protein degradation. It is hoped to be able to influence the degeneration of peripheral nerves by inhibiting this system. To display the events of the WD in vitro, a time series of tissue cultures without inhibitor over a period of eight days is first made. Cultures are compared with and without the addition of peritoneal macrophages. Lactacystin and MG132 are used as proteasome inhibitors for the actual experiments, the latter is used only in in vitro co-cultures of nerve pieces and peritoneal macrophages. In vivo, MG132 is applicated intraperitoneally in different concentrations or by using a gelatin sponge. The results of the in vitro time series show a progressive degeneration of the distal nerve pieces with progressive loss of myelin and axons with a simultaneous increase in phagocytosis by macrophages. The in vitro application of a higher concentration of MG132 shows macrophage inhibitory and neuroprotective effects. Lactacystin shows total rather less effect on both macrophages and on myelin and axons, so its use was abandoned in vivo. In vivo, the results for the preservation of axons by MG132 also are very clear whilst the studied parameters for macrophages remain largely unaffected by the proteasome inhibitor. The systemic administration shows a concentration dependent effect, which implies an activity optimum at a certain concentration, while local application showed a strong effect on the preservation of axons using gelatin sponge. The results confirm the central role of macrophages in the degeneration of peripheral nerves. On the other hand they show differences of the degeneration operations when proteasome inhibitors are used in vivo or in vitro. For more future applications of inhibitors the findings in this paper show that a careful review of the application form is required to increase the prospects of success in malignant diseases. Here, more detailed studies to evaluate the dose-response relationship, particularly in vivo would be necessary. For a therapeutic approach to degenerative disease or regeneration after traumatic events these substances promise yet another potential application in the future.	de
dc.contributor.coReferee	Lingor, Paul PD Dr.	de
dc.contributor.thirdReferee	Mausberg, Rainer Prof. Dr.	de
dc.subject.ger	Wallersche Degeneration	de
dc.subject.ger	MG132	de
dc.subject.ger	Lactacystin	de
dc.subject.ger	Ubiquitin-Proteasom-System	de
dc.subject.ger	UPS	de
dc.subject.ger	Ischiasnerv	de
dc.subject.eng	wallerian degeneration	de
dc.subject.eng	ubiquitin-proteasome-system	de
dc.subject.eng	MG132	de
dc.subject.eng	Lactacystin	de
dc.subject.eng	sciatic nerve	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BAFB-8-7	de
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.description.embargoed	2013-09-11	de
dc.identifier.ppn	756531608	de

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Human- und Zahnmedizin [2870]

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