| dc.contributor.advisor | Sereda, Michael Werner Prof. Dr. | |
| dc.contributor.author | Epplen, Dirk Benedikt | |
| dc.date.accessioned | 2023-06-05T08:35:35Z | |
| dc.date.available | 2023-06-15T00:50:11Z | |
| dc.date.issued | 2023-06-05 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14705 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-9916 | |
| dc.format.extent | 90 | de |
| dc.language.iso | deu | de |
| dc.subject.ddc | 610 | de |
| dc.title | Experimentelle Therapie eines Mausmodells für die Pelizaeus-Merzbacher-Erkrankung mit Lonaprisan und Curcumin | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Metz, Imke Prof. Dr. | |
| dc.date.examination | 2023-06-08 | de |
| dc.description.abstracteng | Pelizaeus-Merzbacher disease (PMD) is a severe x-linked leukodystrophy caused, in the majority of
cases, by a duplication of Plp1 coding for Proteolipid Protein. Using a PMD mouse model carrying
additional copies of Plp1 we investigated whether the progesterone antagonist Lonaprisan or
curcumin ameliorate the course of the disease. During 10 weeks of placebo-controlled treatment
with daily injections of Lonaprisan or curcumin diet motor phenotype was measured followed by
mRNA expression and histological analysis of the central nervous system at the end of study.
Lonaprisan reduced toxic overexpression of Plp1 mRNA in total brain and improved motor
coordination. PMD mice displayed less microgliosis, astrocytosis and lymphocyte infiltration after
Lonaprisan treatment. Moreover, Plp1 mRNA expression correlated inversely to the number of
myelinated axons and the motor phenotype. Curcumin improved motor performance and preserved
myelinated axons in the corticospinal tract of the spinal cord. Curcumin diet reduced the
inflammatory response compared to Plp1 placebo controls. Curcumin did not affect increased Plp1
mRNA levels. These results indicate that PMD mice benefitted from Lonaprisan through a reduction
of toxic Plp1 mRNA overexpression and the effect of curcumin was independent of Plp1 mRNA
expression. | de |
| dc.contributor.coReferee | Meyer, Thomas Prof. Dr. | |
| dc.subject.eng | Pelizaeus-Merzbacher disease | de |
| dc.subject.eng | Lonaprisan | de |
| dc.subject.eng | curcumin | de |
| dc.subject.eng | myelin | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14705-2 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Neuroanatomie, Neurophysiologie, Neuropathologie (PPN619876255) | de |
| dc.description.embargoed | 2023-06-15 | de |
| dc.identifier.ppn | 1847611672 | |
| dc.notes.confirmationsent | Confirmation sent 2023-06-05T08:45:01 | de |