This 2021 rodent study investigated sulforaphane effects on depression:

“Activation of Nrf2 by sulforaphane (SFN) showed fast-acting antidepressant-like effects in mice by:

• Activating BDNF;
• Inhibiting expression of its transcriptional repressors (HDAC2 [histone deacetylase 2, a negative regulator of neuroplasticity], mSin3A, and MeCP2); and
• Revising abnormal synaptic transmission.

In a mouse model of chronic social defeat stress (CSDS), protein levels of Nrf2 and BDNF in the medial prefrontal cortex and hippocampus were lower than those of control and CSDS-resilient mice. In contrast, protein levels of BDNF transcriptional repressors in CSDS-susceptible mice were higher than those of control and CSDS-resilient mice.

These data suggest that Nrf2 activation increases expression of Bdnf and decreases expression of its transcriptional repressors, which result in fast-acting antidepressant-like actions. Furthermore, abnormalities in crosstalk between Nrf2 and BDNF may contribute to the resilience versus susceptibility of mice against CSDS.

Nrf2-induced BDNF transcription in a model of depression.

• Stress inhibits Nrf2 expression, which inhibits BDNF transcriptional and leads to abnormal synaptic transmission, causing depression-like behaviors in mice.
• SFN induces BDNF transcription by activating Nrf2 and correcting abnormal synaptic transmission, resulting in antidepressant-like effects.

In conclusion:

1. Nrf2 regulates transcription of Bdnf by binding to its exon I promoter.
2. Inhibition of Nrf2-induced Bdnf transcription may play a role in the pathophysiology of depression.
3. Activation of Nrf2-induced Bdnf transcription promoted antidepressant-like effects.
4. Alterations in crosstalk between Nrf2 and BDNF may contribute to resilience versus susceptibility after stress.”

https://www.nature.com/articles/s41398-021-01261-6 “Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents”

Part 2 curates three papers that cited this study.

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