In vivo approach to myelin turnover and oligodendrocyte-dependent axonal integrity

Lüders, Katja

dc.contributor.advisor	Werner, Hauke PD Dr.
dc.contributor.author	Lüders, Katja
dc.date.accessioned	2018-10-15T11:57:12Z
dc.date.available	2018-10-15T11:57:12Z
dc.date.issued	2018-10-15
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-002E-E4CC-A
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7090
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	In vivo approach to myelin turnover and oligodendrocyte-dependent axonal integrity	de
dc.type	doctoralThesis	de
dc.contributor.referee	Brose, Nils Prof. Dr.
dc.date.examination	2018-08-21
dc.description.abstracteng	Deletion of the most abundant protein of CNS myelin, proteolipid protein (PLP) causes type 2 spastic paraplegia (SPG2) in humans, which is characterized by axonal degeneration. The assumption that the primary cause of SPG2 is the lack of PLP from oligodendrocytes has been challenged by studies reporting Plp gene products (official gene name Plp1) also in a subset of neurons. To clarify the cellular origin of SPG2, we established mice with a floxed Plp allele to selectively delete Plp in neurons or oligodendrocytes. Recombination of Plp in excitatory projection neurons did not cause neuropathology, whereas oligodendroglial deletion of Plp caused the complete neurodegenerative spectrum observed in Plpnull/Y mice including axonopathy, gliosis and elevated numbers of T cells in the brain and thus provide a novel model of SPG2. We conclude that the primary cause of SPG2 is the lack of PLP in oligodendrocytes. To better understand the interplay of PLP-deficient oligodendrocytes, axons and T cells, we analyzed the emergence of neuropathological events upon Plp-deletion over time in tamoxifen-inducible Plp knockout mice. Importantly, axonal spheroids were observed prior to elevated numbers of T cells, implying that axonopathy occurs independent from T cells in this model, at least initially. Together, by analyzing novel mouse models of SPG2 this work provides relevant information about the cellular neuropathology caused by PLP-deficiency.	de
dc.contributor.coReferee	Flügel, Alexander Prof. Dr.
dc.contributor.thirdReferee	Hörner, Michael Prof. Dr.
dc.contributor.thirdReferee	Göpfert, Martin Prof. Dr.
dc.contributor.thirdReferee	Brück, Wolfgang Prof. Dr.
dc.subject.eng	Proteolipid protein (PLP)	de
dc.subject.eng	Oligodendrocyte	de
dc.subject.eng	Axonopathy	de
dc.subject.eng	Glia-axonal support	de
dc.subject.eng	Hereditary spastic paraplegia type 2 (SPG2)	de
dc.subject.eng	Myelin	de
dc.subject.eng	Neurodegeneration	de
dc.subject.eng	Neuroinflammation	de
dc.subject.eng	Tamoxifen	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E4CC-A-6
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	1032769289

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1112]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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