Work

Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription

Year: 2021

Type: article

Abstract: Background: Accumulating evidence suggested that sulforaphane (SFN) showed prevention effects in stressed mice by activating the NF-E2-related factor-2 (Nrf2). However, the mechanism remains poorly understood. The present study aimed to investigate whether the prevention effects of SFN in stressed mice by activating brain-derived neurotrophic factor (BDNF) transcription on the microglial and revising abnormal dendritic spine morphology. Methods: In vitro study, we performed the Luciferase assay, Chromatin immunoprecipitation assay, Immunofluorescence, and Western blot to investigate whether SFN could activate Nrf2, resulting in BDNF transcription on the BV2 cell. In vivo study, we employed the Social defeat stress mice model, Behavior test, Western blots, Immunofluorescence, and Enzyme-linked immunosorbent assay to further explore whether the prevention effects of SFN in stressed mice by activating BDNF transcription on the microglial and revising abnormal dendritic spine morphology.Results: First, we found that SFN could activate Nrf2, resulting in Nrf2 binding to the BDNF exon I promoter, leading to BDNF protein expression on the BV2 cell. Second, SFN attenuated the decreased levels of Nrf2, and increased levels of MeCP2 expression, revising abnormal BDNF expression in the stressed mice. Third, we further found that the SFN could attenuate the decreased levels of Nrf2 and increased levels of MeCP2 expression on the microglial and revising microglial dysfunction in the stressed mice. Fourth, SFN could attenuate the increased levels of pro-inflammatory cytokine and the decreased levels of anti-inflammatory cytokine release in the stressed mice. Finally, SFN showed prevention effects and revised abnormal dendritic spine morphology in the stressed mice. Conclusions: Therefore, the prophylactic effects of SFN in the stressed mice by activating BDNF transcription on the microglial and revising abnormal dendritic spine morphology.

Source: Acta Pharmacologica Sinica

DOI: 10.1038/s41401-021-00727-z