Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and bench research with no human data
PubMed 33627628 · doi:10.1038/s41398-021-01261-6
What was done
Investigators examined the molecular crosstalk between the transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) in mice. They tested whether Nrf2 regulates Bdnf transcription via its exon I promoter, and evaluated behavioral, electrophysiological, and biochemical changes following Nrf2 activation with sulforaphane (SFN) in wild-type and Nrf2 knockout mice. They also analyzed protein expression of Nrf2, BDNF, and transcriptional repressors (HDAC2, mSin3A, MeCP2) in the medial prefrontal cortex (mPFC) and hippocampus of mice exposed to chronic social defeat stress (CSDS).
What was found
The abstract reports no numerical values, statistical metrics, or sample sizes. Qualitatively, Nrf2 bound to the Bdnf exon I promoter to regulate transcription. Sulforaphane produced fast-acting antidepressant-like behavioral effects, activated BDNF, inhibited transcriptional repressors (HDAC2, mSin3A, and MeCP2), and corrected abnormal synaptic transmission in wild-type mice, but lacked these effects in Nrf2 knockout mice. In the CSDS paradigm, stress-susceptible mice had lower levels of Nrf2 and BDNF, and higher levels of BDNF transcriptional repressors, compared to control and resilient mice.
Why it matters
This study outlines a mechanistic pathway through which Nrf2 directly promotes BDNF expression and suppresses BDNF transcriptional inhibitors, highlighting the Nrf2-BDNF axis as a biological contributor to stress resilience and a candidate target for rapid-acting antidepressant strategies.
Limits
The findings are derived entirely from rodent and molecular models; applicability to human major depressive disorder remains unproven. The abstract does not report sample sizes, dosing regimens, effect sizes, or quantitative confidence intervals.
Cited by
- supports Sulforaphane upregulates brain-derived neurotrophic factor (BDNF).