Ambiguous Contribution of Glucocorticosteroids to Acute Neuroinflammation in the Hippocampus of Rat

Autor: Liya V. Tret’yakova, Alexey A. Kvichansky, Ekaterina S. Barkovskaya, Anna O. Manolova, Alexey P. Bolshakov, Natalia V. Gulyaeva
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 13, p 11147 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms241311147
Popis: Effects of modulation of glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) on acute neuroinflammatory response were studied in the dorsal (DH) and ventral (VH) parts of the hippocampus of male Wistar rats. Local neuroinflammatory response was induced by administration of bacterial lipopolysaccharide (LPS) to the DH. The modulation of GR and MR was performed by dexamethasone (GR activation), mifepristone, and spironolactone (GR and MR inhibition, respectively). Experimental drugs were delivered to the dentate gyrus of the DH bilaterally by stereotaxic injections. Dexamethasone, mifepristone, and spironolactone were administered either alone (basal conditions) or in combination with LPS (neuroinflammatory conditions). Changes in expression levels of neuroinflammation-related genes and morphology of microglia 3 days after intrahippocampal administration of above substances were assessed. Dexamethasone alone induced a weak proinflammatory response in the hippocampal tissue, while neither mifepristone nor spironolactone showed significant effects. During LPS-induced neuroinflammation, GR activation suppressed expression of selected inflammatory genes, though it did not prevent appearance of activated forms of microglia. In contrast to GR activation, GR or MR inhibition had virtually no influence on LPS-induced inflammatory response. The results suggest glucocorticosteroids ambiguously modulate specific aspects of neuroinflammatory response in the hippocampus of rats at molecular and cellular levels.
Databáze: Directory of Open Access Journals
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