Dexamethasone Modulates Lipopolysaccharide-Induced Expression of Proinflammatory Cytokines in Rat Hippocampus

Tret’yakova, L. V.; Kvichansky, A. A.; Bolshakov, A D; Gulyaeva, N. V.

doi:10.1134/s1819712421330011

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…The predominance of activated forms of microglia in the DH also confirmed the development of neuroinflammation. Proinflammatory effects of GCS at high concentrations were previously demonstrated in several studies [17][18][19], and we recently extended previous findings by showing that direct application of DEX to the hippocampal tissue had similar proinflammatory effect [20].…”

Section: Discussionsupporting

confidence: 84%

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

Tret’yakova,

Kvichansky,

Barkovskaya

et al. 2023

IJMS

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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.

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Section: Discussionsupporting

confidence: 84%

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

Tret’yakova,

Kvichansky,

Barkovskaya

et al. 2023

IJMS

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“…These data indicate a dual role of glucocorticoids in hippocampal neuroinflammation (either anti- or pro-inflammatory), though conditions promoting these opposite situations—as well as gene-related mechanisms—remain obscure [ 52 ]. Using dexametasone as a reference glucocorticoid, Tret’yakova et al demonstrated that, injected intrahippocampally, it was able to induce only weak neuroinflammation, but when applied during LPS-induced neuroinflammation, dexametasone significantly influenced cytokine balance in the hippocampus [ 53 ]. Stress-related gene Hspb1 upregulated after both MCAO and LPS in our study was found among the key genes correlated with ischemic injury [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

et al. 2021

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Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to “positive regulation of tumor necrosis factor biosynthetic process”, “cell adhesion”, “TNF signaling pathway”, and “phagosome” as compared with non-responding ones. In contrast, positive and negative “regulation of cell proliferation” and “HIF-1 signaling pathway” mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia.

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Brain Trauma, Glucocorticoids and Neuroinflammation: Dangerous Liaisons for the Hippocampus

Komoltsev

Gulyaeva

2022

Biomedicines

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Glucocorticoid-dependent mechanisms of inflammation-mediated distant hippocampal damage are discussed with a focus on the consequences of traumatic brain injury. The effects of glucocorticoids on specific neuronal populations in the hippocampus depend on their concentration, duration of exposure and cell type. Previous stress and elevated level of glucocorticoids prior to pro-inflammatory impact, as well as long-term though moderate elevation of glucocorticoids, may inflate pro-inflammatory effects. Glucocorticoid-mediated long-lasting neuronal circuit changes in the hippocampus after brain trauma are involved in late post-traumatic pathology development, such as epilepsy, depression and cognitive impairment. Complex and diverse actions of the hypothalamic–pituitary–adrenal axis on neuroinflammation may be essential for late post-traumatic pathology. These mechanisms are applicable to remote hippocampal damage occurring after other types of focal brain damage (stroke, epilepsy) or central nervous system diseases without obvious focal injury. Thus, the liaisons of excessive glucocorticoids/dysfunctional hypothalamic–pituitary–adrenal axis with neuroinflammation, dangerous to the hippocampus, may be crucial to distant hippocampal damage in many brain diseases. Taking into account that the hippocampus controls both the cognitive functions and the emotional state, further research on potential links between glucocorticoid signaling and inflammatory processes in the brain and respective mechanisms is vital.

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Dexamethasone Modulates Lipopolysaccharide-Induced Expression of Proinflammatory Cytokines in Rat Hippocampus

Cited by 4 publications

References 20 publications

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

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

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

Brain Trauma, Glucocorticoids and Neuroinflammation: Dangerous Liaisons for the Hippocampus

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