Show simple item record

AuthorLattke, Michaeldc.contributor.author
Date of accession2016-03-15T09:04:48Zdc.date.accessioned
Available in OPARU since2016-03-15T09:04:48Zdc.date.available
Year of creation2012dc.date.created
AbstractNeuroinflammation is an essential defense response to pathogens or injury in the central nervous system, but might also contribute to the pathogenesis of neurological disorders. Astrocytes are glial cells that are implicated in neuroinflammation, but also in brain development and homeostasis. The NF-kappa B transcription factors are key regulators of inflammation that also regulate in cell proliferation, differentiation and survival. Previous studies suggested that NF-kappa B activation in astrocytes might indeed be critical for neuroinflammatory responses and its pathological consequences. In the present study a novel mouse model was characterized to further elucidate the role of astroglial NF-Kappa B signaling in neuroinflammation. This model conditionally expresses a constitutively active mutant of the NF-kappa B activating kinase IKK2 in astrocytes. This results in astroglial NF-kappa B activation, which is sufficient to induce a prominent neuroinflammatory response and impairs brain development and homeostasis. When astroglial NF-kappa B was activated during brain development, this resulted in hydrocephalus formation due to impaired ependymal ciliogenesis. Activation of astroglial NF-kappa B in the mature brain resulted in cerebellar ataxia due to excitotoxic Purkinje cell degeneration caused by a disrupted support function of the astrocyte-related Bergmann glia. In conclusion, the present study strengthens the view that astrocytes along with microglia are key players of the innate immunity of the central nervous system. The study also provides the first causal link between NF-kappa B signaling and hydrocephalus formation and indicates that NF-kappa B mediated astrogliotic activation of Bergmann glia might cause degeneration of Purkinje cells in autoimmune/inflammatory cerebellar ataxias. As future perspective, the described mouse model might serve as useful tool to study hydrocephalus formation, autoimmune/inflammatory ataxias, and the role of inflammatory processes in other neurological diseases.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandarddc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v3dc.rights.uri
KeywordNeuroinflammationdc.subject
KeywordPurkinje cell degenerationdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHAstrocytesdc.subject.mesh
MeSHNF-kappa Bdc.subject.mesh
MeSHPurkinje cellsdc.subject.mesh
TitleFunctional analysis of astroglial IKK/NF-KappaB signaling in brain development and homeostasisdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-2591dc.identifier.doi
PPN1651948747dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-82933dc.identifier.urn
GNDAstrozytdc.subject.gnd
GNDHomöostasedc.subject.gnd
GNDHydrocortisondc.subject.gnd
FacultyFakultät für Naturwissenschaftenuulm.affiliationGeneral
Date of activation2013-01-07T07:58:20Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionW: W-H 13.158uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID8293uulm.vtsID
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record