2. Academic Validation
  3. Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription

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

  • Acta Pharmacol Sin. 2022 Apr;43(4):829-839. doi: 10.1038/s41401-021-00727-z.
Rui Tang  # 1 2,  Qian-Qian Cao  # 1,  Sheng-Wei Hu  # 3,  Lu-Juan He 1,  Peng-Fei Du 4,  Gang Chen 5,  Rao Fu 6,  Fei Xiao 7,  Yi-Rong Sun 8,  Ji-Chun Zhang 9,  Qi Qi 10
Affiliations

Affiliations

  • 1 Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
  • 2 School of Medicine, Xi-an Medicine College, Xi-an, 710000, China.
  • 3 MOE Key Laboratory of Tumor Molecular Biology, Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China.
  • 4 Second Affiliated Hospital of Jiaxing, Jiaxing, 4564496, China.
  • 5 School of traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
  • 6 Department of Anatomy, School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080, China.
  • 7 Department of Pharmacology, School of Pharmacy, Jinan University, Guangzhou, 510632, China.
  • 8 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. sun_yirong@gibh.ac.cn.
  • 9 Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China. jczhang@jnu.edu.cn.
  • 10 MOE Key Laboratory of Tumor Molecular Biology, Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China. qiqikc@jnu.edu.cn.
  • # Contributed equally.
PMID: 34272506 DOI: 10.1038/s41401-021-00727-z
Abstract

Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.

Keywords

BDNF; Nrf2; microglia; stress resilience; sulforaphane.

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