Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kriegl, L.
Microglial activation in mouse brain following peripheral immune stimulation.
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2020. pp. 68
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Farzi Aitak
- Holzer Peter
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- Abstract:
- Emerging evidence indicates that inflammatory processes may be involved in the development of neuropsychiatric disorders. However, while underlying mechanisms are not yet fully understood, previous work in rodents has shown that peripheral immune stimulation by both viral and bacterial factors evokes neuroinflammatory processes. This “mirroring” effect is characterized by an enhanced expression of cytokines in the murine brain, behavioral signs of sickness and depressive-like behavior at a time point when acute sickness has abated. In this context, microglial cells are thought to play a crucial role. They are resident macrophages and constant monitors of brain tissue playing a key role in conserving CNS integrity. Furthermore, Neuropeptide Y (NPY), which is one of the most prevalent peptides in the central nervous system, is thought to counteract such a negative impact of immune stimulation on mood and stress resilience. This homeostatic role of NPY might arise from its capability to influence the activation of microglial cells, which is induced by immune activation. The aims of this diploma thesis were to characterize hypothalamic microglial cell activation evoked by bacterial and viral peripheral immune stimulation and the possible impact of intranasally (IN) applied NPY at two time points: 3h post peripheral immune challenge (short term) and 21h post peripheral immune challenge (long term). Therefore, mice were infused IN with water or NPY and 30 minutes thereafter, intraperitoneally (IP) injected with either the bacterial cell-wall component lipopolysaccharide (LPS) or the viral mimic Poly(I:C). Brains were microdissected and RNA was extracted from hypothalamic areas. Gene expression of microglial markers Iba1 and polarization markers CD86 (M1) and CD206 (M2) were evaluated via qPCR. Two-way analysis of variance (ANOVA) was performed for statistical analysis, followed by post-hoc planned comparison with Fisher’s Least Significant Difference (LSD) test. Interestingly, in the short term paradigm 3h after application, the strongest upregulation of all three markers Iba1 (p=0.0056), CD206 (p=0.0033) and CD86 (p=0.0019) was found after the combined injection of NPY and Poly(I:C). Poly(I:C) and LPS also led to an upregulation of both the more pro-inflammatory marker CD86 (p=0.0504 and p=0.0104) and the more anti-inflammatory marker CD206 (p=0.455 and p=0.0282). In the groups 21h after application only CD206 in the water + Poly(I:C) and NPY + Poly(I:C) combination was still upregulated. These results underline previous findings of strong stimulation of microglial cells following peripheral immune stimulation. In conclusion and contrary to the hypothesis under study, IN NPY application failed to mitigate microglial marker expression in the hypothalamus following peripheral immune stimulation by LPS or Poly(I:C).