dc.contributor.advisor | Brück, Wolfgang Prof. Dr. | |
dc.contributor.author | Gertig, Ulla | |
dc.date.accessioned | 2016-12-16T09:36:57Z | |
dc.date.available | 2016-12-16T09:36:57Z | |
dc.date.issued | 2016-12-16 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002B-7CE3-5 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-6043 | |
dc.language.iso | deu | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 610 | |
dc.title | Constitutive heterogeneity and response diversity of microglia in pathological conditions | de |
dc.type | doctoralThesis | de |
dc.contributor.referee | Brück, Wolfgang Prof. Dr. | |
dc.date.examination | 2016-12-12 | |
dc.description.abstracteng | Microglia, resident myeloid cells of the CNS, execute an enormous variety of different functions
like tissue surveillance, nursing of synapses, phagocytosis of foreign material or debris, and initiation
of appropriate immune responses upon CNS infection and damage (Hanisch and Kettenmann,
2007; Kettenmann et al., 2011). The duration of an immune response is thereby selflimiting
as it resolves with a successful combat of the threat. A sustaining threat, however, can
lead to an over-activation of microglia which switches their initially beneficial effect to a rather
detrimental outcome. This disturbed microglia phenotype leads to a variety of neuropsychiatric
disorders or neurodegenerative diseases and aggravates the disease outcomes, mostly resulting
in neurotoxicity (Gold and Khoury, 2015; Hickman et al., 2008; von Bernhardi et al., 2015). Targeting
microglia is therefore a promising therapeutic approach to oppose those diseases (Chen
et al., 2014;Wes et al., 2016). Though,microglia functions are inmost cases performed by amere
subpopulation, a drug targeting the whole microglia population would thereby effect not only
the subsets causing the neurotoxicity but also the subsets which try to resolve the disease (Biber
et al., 2016; Marshall et al., 2014; Olah et al., 2012; Venkatesan et al., 2010). Thus, to develop
a useful drug, which specifically targets a harmful subpopulation of microglia, the microglial
organization principle needs to be unraveled beforehand.
This study focused on the functional heterogeneity of a microglial immune response by investigating
cytokine producing microglia subsets confronted with a variety of stimuli conditions in
different environmental contexts. I observed a highly specific adaptation of those subsets. The
degree of adaptation is thereby dependent on the investigated function, the used stimulus, the
stimulus intensity and the microglia density. Further analysis revealed that the subpopulations
are not performing one single function butmultiple functions at once. Function specific subpopulations
are thereby composed of subpopulations which perform other functions as well. These
results demonstrate an almost infinite organization complexity ofmicroglia subsets, highlighting
the importance of further research to fully understand the nature of microglia. | de |
dc.contributor.coReferee | Ehrenreich, Hannelore Prof. Dr. Dr. | |
dc.contributor.thirdReferee | Wouters, Fred Prof. Dr. | |
dc.contributor.thirdReferee | Gärtner, Jutta Prof. Dr. | |
dc.contributor.thirdReferee | Werner, Hauke Dr. | |
dc.contributor.thirdReferee | Heinrich, Ralf Prof. Dr. | |
dc.subject.eng | Microglia | de |
dc.subject.eng | Hetereogeneity | de |
dc.subject.eng | in vitro | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002B-7CE3-5-6 | |
dc.affiliation.institute | Medizinische Fakultät | |
dc.subject.gokfull | Medizin (PPN619874732) | de |
dc.subject.gokfull | Neuroanatomie, Neurophysiologie, Neuropathologie (PPN619876255) | de |
dc.identifier.ppn | 875067646 | |