Microglia, the brain’s resident immune cells, exhibit constitutive expression of the ionized calcium-binding adaptor molecule 1 (IBA1). They are long-lived cells that exhibit a senescent morphology (dystrophy) with aging. It has been reported that dystrophy of IBA1-positive microglia is exacerbated in obese humans. Furthermore, we detected another microglial abnormality, which is the loss of IBA1 immunoreactivity that can create large areas in the brain seemingly devoid of all microglial cells. Here, we systematically compared microglial appearance in human hippocampi derived from obese individuals compared to controls by morphological and spatial analysis. In both groups, areas that were negative for IBA1 contained P2YR12 and glutathione-peroxidase 1 (GPX)-positive microglia. The number and extent of IBA1-negative regions was increased in obese cases. Since some cases of non-obese individuals also exhibited loss of IBA-1 immunoreactivity, we searched for possible confounders and found that hepatic dysfunction strongly impacts the distribution of microglial cells: a spatial analysis of scanned IBA1-stained sections increased Mean Empty Space distances (p=0.016) and IBA1-negative areas (p=0.090) which were independent of the cause of liver dysfunction, but also from aging, were detected. Thus, we report on a novel type of microglia pathological change, i.e. localized loss of IBA1 that is linked, at least in part, to obesity and hepatic dysfunction.:1 Introduction . . . . .. . . . . . . . .. . . . . . . . . . .. 2
1.1 Formation and morphology. .. . . . . . . . . . 2
1.2 Microglia and aging . . . . . . . . . . . . . . . . . 3
1.3 Microglia and obesity . . . . . . . .. . . . .. . . .5
1.4 Hippocampus . . . . . . . . . . . . . . . . . .. . . . 6
1.5 IBA1 . . . . . . . . . . . . . . . . . . . . . . . . .. . . . 7
1.6 Microglial markers . . . . . . . . . . . . .. . . . . 9
1.7 Hepatic dysfunction. . . . . . . . . . . . . . . . .10
1.8 Hepatic encephalopathy . . . . . . . . . . . . .10
1.9 Microglia in hepatic encephalopathy . . . 11
2 Aims and outlines of the dissertation . . . . .13
3 Manuscript of publication . . . . . . . . . . .. . . 15
4 Abstract . . . . . . . . . . .. . . . . . . . . . .. . . . . .25
5 Bibliography. . . . . . . . . . .. . . . . . . . . . .. . . 29
6 Appendix . . . . . . . . . . .. . . . . . . . . . .. . . . . 38
6.1 Supplemental Material .. . . . . . . . . . . . .. 38
7 Darstellung des eigenen Beitrags . . . . . . . 41
8 Erklärung über die eigenständige
Abfassung der Arbeit . . . . . . . . . . .. . . . . .. . 42
10 Publications . . . . . . . . . . .. . . . . . . . . . . . .45
11 Acknowledgements. . . . . . . . . . .. . . . . . . 46
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:38389 |
| Date | 18 February 2020 |
| Creators | Lier, Julia |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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