Universität zu Köln

Olschewski, Daniel Navin ORCID: 0009-0008-8429-5382, Nazarzadeh, Nilufar, Lange, Felix, Koenig, Anna Maria, Kulka, Christina, Abraham, Jella-Andrea, Blaschke, Stefan Johannes ORCID: 0000-0001-8643-3824, Merkel, Rudolf ORCID: 0000-0003-3178-3282, Hoffmann, Bernd ORCID: 0000-0002-3803-8835, Fink, Gereon Rudolf ORCID: 0000-0002-8230-1856, Schroeter, Michael ORCID: 0000-0001-8441-4793, Rueger, Maria Adele ORCID: 0000-0001-8036-395X and Vay, Sabine Ulrike ORCID: 0000-0002-3289-7807 (2024). 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. BMC Neuroscience, 25 (1). pp. 1-19. Springer Nature. ISSN 1471-2202

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Abstract

[Artikel-Nr.: 29] Background: Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting. The renin–angiotensin–aldosterone system regulates arterial blood pressure through endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2 receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensin II 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 oxygen and glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effects on microglia and cortical neurons. Result: The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes during ischemic 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 resulted in both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reduced the 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 healthy and ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this work emphasizes the strong interference of the different cells in the CNS and that targeting astrocytes might serve as a therapeutic strategy to influence the acting of glia-neuronal network in de- and regenerative context.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Olschewski, Daniel Navin UNSPECIFIED https://orcid.org/0009-0008-8429-5382 UNSPECIFIED Nazarzadeh, Nilufar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lange, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Anna Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kulka, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Abraham, Jella-Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan Johannes UNSPECIFIED https://orcid.org/0000-0001-8643-3824 UNSPECIFIED Merkel, Rudolf UNSPECIFIED https://orcid.org/0000-0003-3178-3282 UNSPECIFIED Hoffmann, Bernd UNSPECIFIED https://orcid.org/0000-0002-3803-8835 UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED https://orcid.org/0000-0002-8230-1856 UNSPECIFIED Schroeter, Michael UNSPECIFIED https://orcid.org/0000-0001-8441-4793 UNSPECIFIED Rueger, Maria Adele UNSPECIFIED https://orcid.org/0000-0001-8036-395X UNSPECIFIED Vay, Sabine Ulrike UNSPECIFIED https://orcid.org/0000-0002-3289-7807 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-815710
Identification Number:	10.1186/s12868-024-00876-x
Journal or Publication Title:	BMC Neuroscience
Volume:	25
Number:	1
Page Range:	pp. 1-19
Number of Pages:	19
Date:	26 June 2024
Publisher:	Springer Nature
ISSN:	1471-2202
Language:	English
Faculty:	External institution Faculty of Medicine
Divisions:	Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich Faculty of Medicine > Neurologie > Klinik und Poliklinik für Neurologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Neuroinflammation ; Astrocytes, Microglia ; Cortical neuronal network ; Cerebral ischemia ; Renin– angiotensin–aldosterone system ; Microelectrode array ; MEA ; Telmisartan, PD123319 English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81571