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dc.contributor.advisorFriese, Manuel A. (Prof. Dr.)-
dc.contributor.authorWinkler, Iris-
dc.date.accessioned2020-10-20T14:22:08Z-
dc.date.available2020-10-20T14:22:08Z-
dc.date.issued2020-
dc.identifier.urihttps://ediss.sub.uni-hamburg.de/handle/ediss/8564-
dc.description.abstractMultiple sclerosis (MS) is characterized by immune cell infiltration, axonal demyelination and neurodegeneration. Excessive activation of the glutamatergic pathway accompanies MS pathophysiology resulting in neuronal stress response networks with alteration of neuronal signaling, thereby perpetuating neurodegeneration and consecutive neurological deficits. A fundamental mechanism to respond to changes in the cellular environment is coordination of translation by microRNAs (miRNAs). However, it remains unclear to which extend miRNAs orchestrate neuronal gene expression and determine consecutive neurodegeneration in central nervous system (CNS)-inflammation. By targeted profiling of neuronal transcriptome and miRNome in CNS-inflammation it was demonstrated here that genes involved in neuronal regulatory processes and synaptic signaling were significantly underrepresented, while at the same time newly identified inflammation-induced miRNAs were predicted to target these mRNA transcripts. It was shown in this work that miR-92a-3p was highly expressed in healthy motor neurons and transcriptionally upregulated by extracellular glutamate. Luciferase reporter assays validated cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) mRNA as a miR-92a-3p target. Further, deletion of miR-92a-3p in the MS mouse model experimental autoimmune encephalomyelitis (EAE) led to exacerbated neurological disability but unchanged immune cell infiltration, implying a neuronal function of miR-92a-3p induction. Yet, the neuronal substrate of miR-92a-3p deletion that caused exacerbated clinical disability in CNS-inflammation is still to be investigated. In future studies, the interaction network of miR-92a-3p and Cpeb3 and their implications for neuronal survival in CNS-inflammation and glutamate excitotoxicity will be investigated in mouse models and validated in MS patients. Together, this work offers a new approach for deciphering the contribution of miRNA networks to synaptic function and neuronal integrity in CNS-inflammation with possible implications for the treatment of MS-associated neurodegeneration.en
dc.language.isoende_DE
dc.publisherStaats- und Universitätsbibliothek Hamburg Carl von Ossietzky
dc.rightshttp://purl.org/coar/access_right/c_f1cfde_DE
dc.subjectExzitotoxizitätde
dc.subjectNeurodegenerationde
dc.subjectGlutamatde
dc.subjectExperimentelle autoimmune Enzephalomyelitisde
dc.subjectNeuroinflammationde
dc.subjectZNS-Inflammationde
dc.subjectExcitotoxicityen
dc.subjectNeurodegenerationen
dc.subjectGlutamateen
dc.subjectExperimental autoimmune encephalomyelitisen
dc.subjectmotor neuronen
dc.subjectNeuroinflammationen
dc.subjectCNS-inflammationen
dc.subject.ddc570: Biowissenschaften, Biologiede_DE
dc.titleNeuronal microRNAs in inflammation-induced neurodegenerationen
dc.title.alternativeNeuronale microRNAs in inflammationsinduzierter Neurodegenerationde
dc.typedoctoralThesis
dcterms.dateAccepted2020-08-28-
dc.rights.ccNo licensede_DE
dc.rights.rshttp://rightsstatements.org/vocab/InC/1.0/
dc.subject.bcl42.13: Molekularbiologiede_DE
dc.subject.bcl42.15: Zellbiologiede_DE
dc.subject.bcl42.17: Allgemeine Physiologiede_DE
dc.subject.bcl42.20: Genetikde_DE
dc.subject.bcl44.90: Neurologiede_DE
dc.subject.gndMultiple Sklerose
dc.subject.gndmiRNA
dc.subject.gndMotoneuron
dc.subject.gndDegeneration
dc.subject.gndZentralnervensystem
dc.type.casraiDissertation-
dc.type.dinidoctoralThesis-
dc.type.driverdoctoralThesis-
dc.type.statusinfo:eu-repo/semantics/publishedVersionde_DE
dc.type.thesisdoctoralThesisde_DE
tuhh.opus.id10690
tuhh.opus.datecreation2020-09-04
tuhh.type.opusDissertation-
thesis.grantor.departmentBiologiede_DE
thesis.grantor.placeHamburg
thesis.grantor.universityOrInstitutionUniversität Hamburgde_DE
dcterms.DCMITypeText-
dc.identifier.urnurn:nbn:de:gbv:18-ediss-86835-
item.fulltextWith Fulltext-
item.creatorOrcidWinkler, Iris-
item.grantfulltextembargo_20221001-
item.advisorGNDFriese, Manuel A. (Prof. Dr.)-
item.languageiso639-1other-
item.creatorGNDWinkler, Iris-
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen
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