Therapeutischer Einfluss des Radikalfängers Trolox in einem Mausmodell für das Rett-Syndrom: Bewertung oxidativer Stressmarker in zerebralem Gewebe

Hüser, Marc Albert

dc.contributor.advisor	Müller, Michael Prof. Dr.
dc.contributor.author	Hüser, Marc Albert
dc.date.accessioned	2017-05-10T08:32:31Z
dc.date.available	2017-05-30T22:50:09Z
dc.date.issued	2017-05-10
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0023-3E3E-7
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-6289
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Therapeutischer Einfluss des Radikalfängers Trolox in einem Mausmodell für das Rett-Syndrom: Bewertung oxidativer Stressmarker in zerebralem Gewebe	de
dc.type	doctoralThesis	de
dc.title.translated	Therapeutic impact of the free-radical scavenger Trolox in a mouse model of Rett-syndrome: Assessment of oxidative stress marker in cerebral tissue	de
dc.contributor.referee	Müller, Michael Prof. Dr.
dc.date.examination	2017-05-23
dc.description.abstracteng	The aim of this work was to assess a variety of phenotypic and biochemical features in a mouse model of Rett-syndrome, which was treated in vivo with the free radical scavenger Trolox. Rett-syndrome is a postnatal progressive neurological developmental disorder. At present a cure is not available. It has been known for long that blood samples of Rett patients show reduced vitamin E levels. Also, unbalanced levels of reactive oxygen species (ROS) are a critical aspect of this disorder. Accordingly, the in vivo vitamin E supplementation with the antioxidant Trolox, represents a plausible therapeutic approach, which has already been successfully tested in isolated brain tissue of these mice. The analyses carried out in this thesis represent only part of a detailed preclinical testing of antioxidants for the treatment of Rett syndrome, which is currently conducted in the hosting lab. Accordingly, the overall view of all experiments carried out within the framework of this project is important. The major focus of my thesis was to establish two biochemical methods - the protein carbonylation assay and the lipid peroxidation measurements in isolated brain tissue. In addition, mitochondrial membrane potentials were monitored photometrically, the behavior of the treated mice was tested, and the morphological tissue structure was analyzed by Nissl staining. After systemic Trolox treatment, significant changes could be detected for some of tested parameters. In particular, the extent of lipid peroxidation in frontal cortex was reduced and the exploratory activity of the Mecp2-/y mice was improved. However, in part Trolox had also inverse effects on wildtype mice, suggesting an extremely sensitive redox balance and emphasizing the importance of a careful antioxidant dosing. Furthermore, clear indications for handling effects became evident in the mice which were treated for several weeks. This issue needs to be addressed in the future by optimizing study design. For example, an application of drug substances via food may be considered to rule out such unwanted handling effects. Furthermore, the exact blood-brain barrier permeation of Trolox may be a limiting factor. Therefore, a combination of vitamin E compounds for example with vitamin C could be considered, since the recovery of vitamin E is directly related to the availability of vitamin C. As a result, synergistic effects and an improved drug efficiency may be expected.	de
dc.contributor.coReferee	Wouters-Bunt, Freddy Prof. Dr.
dc.subject.eng	Trolox	de
dc.subject.eng	reactive oxygen species (ROS)	de
dc.subject.eng	antioxidant treatment	de
dc.subject.eng	oxidative stress	de
dc.subject.eng	mitochondrial dysfunction	de
dc.subject.eng	oxidative tissue damage	de
dc.subject.eng	mouse behavior	de
dc.subject.eng	Rett-syndrome	de
dc.subject.eng	vitamin E	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3E3E-7-7
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Neuroanatomie, Neurophysiologie, Neuropathologie (PPN619876255)	de
dc.description.embargoed	2017-05-30
dc.identifier.ppn	886542804

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