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| Hauptseite > Publikationsdatenbank > The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke |
| Hauptseite > Publikationsdatenbank > The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke |
| Journal Article | FZJ-2024-04902 |
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2024
Springer
Heidelberg
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Please use a persistent id in citations: doi:10.1186/s12868-024-00876-x doi:10.34734/FZJ-2024-04902
Abstract: AbstractBackground Astrocytes are the most abundant cell type of the central nervous system and are fundamentallyinvolved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on theirneighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specificdifferences in astrocytic acting. The renin–angiotensin–aldosterone system regulates arterial blood pressurethrough endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensinII receptors impact astrocyte function as revealed in an in vitro system mimicking cerebral ischemia.Astrocytes derived from neonatal wistar rats were exposed to telmisartan (angiotensin II type 1 receptor-blocker)or PD123319 (angiotensin II type 2 receptor-blocker) under normal conditions (control) or deprivation from oxygenand glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effectson microglia and cortical neurons.Result The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes duringischemic conditions in vitro without affecting their proliferation rate or disturbing their expression of S100A10,a marker of activation. The inhibition of the angiotensin II type 2 receptor pathway by PD123319 resultedin both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reducedthe expression of pro-inflammatory mediators with simultaneous increase of anti-inflammatory markers in microglia.Increased neuronal activity was observed after treatment of neurons with CM of telmisartan- as well as PD123319-stimulated astrocytes.Conclusion Data show that angiotensin II receptors have functional relevance for astrocytes that differs in healthyand ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this
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