English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Duque EA. Glucocorticoids effects on LPS-induced inflammation in rat primary frontal cortex cultures. [dissertation (Masters thesis in Pharmacology)] – Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo; 2013. The excessive inflammation can be detrimental and can lead to dysfunction and tissue damage, as seen in some diseases such as Alzheimer's and multiple sclerosis. Although glucocorticoids (GCs) are the most commonly worldwide prescribed anti-inflammatory drug, it was shown that increased levels of this hormone can enhance some aspects of inflammation, i.e., LPS (lipopolysaccharide)-induced NFKB activation. In the brain, the cell type where NFKB activation occurs could predict its function. Neuronal NFKB would be beneficial while glial NFKB would be deleterious. In this study we aimed to evaluate the effects of GCs on the LPS-induced NFKB activation at the different cell types (neurons, astrocytes, and microglia) of primary frontal cortex culture derived from newborn Wistar rats. Mixed neuron / glial cells cultures and enriched neurons cultures were previously exposed to corticosterone (CORT, 1 μM, 24h) followed by LPS (10 μg/ml, 1 h). The cell populations in each culture were 72% astrocytes, 22% microglia, and 6% neurons in mixed cultures and 16% astrocytes, 8% microglia, and 76% of neurons in enriched cultures. Neuron and microglia expressed TLR4, the LPS receptor, which was not observed for astrocytes. Using EMSA, we showed that CORT was not classically anti-inflammatory in mixed cultures, since this hormone did not prevent LPS-induced NFKB activation. In the neuronal enriched cultures, none of the treatments activated NFKB. For nuclear RELA localization, we observed that neurons were not responsive to LPS whereas microglia showed strong LPS-induced nuclear RELA imunnostaining. CORT did not modulate LPS-induced effects at neurons or microglia. Comparing mixed and neuronal-enriched cultures, there was no difference on NFKB activation, suggesting that for neurons and microglia, cell interactions was not determinant for this response. At these two cell types, GR signaling seemed important for the physiological maintenance of nuclear RELA, irrespective to CORT or LPS stimuli. Astrocytes from mixed cultures, on the other hand, were highly responsive to LPS-induced NFKB activation, probably to an indirect effect, since these cells were negative to TLR4. CORT did not prevent RELA nuclear translocation which was decreased by RU486, a GR antagonist, revealing a CORT role for the astrocyte maintenance of LPS-induced NFKB activation. Interestingly, astrocytes from neuronal-enriched cultures were less responsive to LPS and in the presence of RU486, they behave likewise neurons and microglia. Our results confirmed that CORT, indeed, is not uniformly anti-inflammatory and that the antior pro-inflammatory actions of CORT are dependent of cell type, cell interactions, GR activation, and GCs levels. Furthermore, we showed that astrocytes, in mixed cultures, are the main target for these selective GC roles.

Efeito dos glicocorticóides na resposta inflamatória induzida por LPS em cultura de células primárias fronto-corticais de ratos neonatos.