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Exploring microglial functions under physiological and pathological conditions by genome-wide expression profiling

Holtman, I. R., 2016, [Groningen]: University of Groningen. 244 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Inge Richelle Holtman
Microglia cells are essential for brain homeostasis and play an important role in neurodegeneration and brain aging. Genes that are important for these microglia functions and activities are transcribed in RNA, which is subsequently translated into protein. With the recent advances in techniques to generate genome-wide RNA expression profiles, it has become possible to study microglia at a whole new level and to delineate the molecular pathways and mechanisms that regulate their function and activity. In this dissertation we present the Glia Open Access Database (GOAD), which is an online database where previously generated genome-wide glia expression profiles were made available to the research community. In addition, we generated RNA expression profiles from microglia from the brains of mice, zebrafish and humans to address research questions related to 1) the effect of aging and neurodegeneration on microglia, 2) interspecies comparability and 3) the role of microglia in the developing brain. When comparing microglia from different mouse models for neurodegeneration and brain aging we observed a highly comparable expression profile, suggesting that microglia contribute to these conditions in a similar way. When performing interspecies comparisons, we found that the physiological microglia expression profiles were relatively similar, but the activation, aging and neurodegeneration profiles differed across species. In the brain development study, we identified a subpopulation of microglia that highly expresses factors that could be crucial for brain development. In summary, this PhD dissertation presents studies where genome-wide expression analysis was used to study microglia in health and disease.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date6-Jun-2016
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-6169-892-6
Publication statusPublished - 2016

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