Here are two papers published after Part 2 that cited the Part 1 rodent study, starting with a 2023 rodent study performed by several Part 1 coauthors:
“We used a low-dose LPS-induced endotoxaemia model to mimic clinical characteristics of sepsis. We found that adolescent LPS treatment was sufficient to increase levels of inflammatory factor TNF-α in both the medial prefrontal cortex (mPFC) and hippocampus at post-natal day P22.
P21 LPS-treated mice were injected with sulforaphane (SFN) or saline intraperitoneally at P49 and then subjected to subthreshold social defeat stress (SSDS). We found that SFN preventative treatment significantly:
- Decreased the social avoidance, anhedonia, and behavioural despair detected by the social interaction test, sucrose preference test, tail suspension test, and forced swim test, respectively.
- Decreased anxiety-like behaviours without affecting locomotor activities.
- Increased Nrf2 and brain-derived neurotrophic factor (BDNF) levels in the mPFC of P21 LPS-treated mice after SSDS compared with saline control mice.
The above results suggest that activation of the Nrf2-BDNF signalling pathway prevents the effect of adolescent LPS-induced endotoxaemia on stress vulnerability during adulthood.
These results suggest that early adolescence is a critical period during which inflammation can promote stress vulnerability during adulthood. This might be due to increased inflammatory response in the mPFC, and mediated by decreased levels of Nrf2 and BDNF. These findings may shed light on the potential use of SFN as an alternative preventative intervention for inflammation-induced stress vulnerability.”
https://link.springer.com/article/10.1007/s00213-022-06285-4 “Lipopolysaccharide-induced endotoxaemia during adolescence promotes stress vulnerability in adult mice via deregulation of nuclear factor erythroid 2-related factor 2 in the medial prefrontal cortex” (not freely available)
This study demonstrated that adolescent diseases and stresses don’t necessarily develop into adult social problems. A timely intervention may even prevent future adult problems.
The one-time 10 mg/kg sulforaphane dose was the same as Part 1’s dose, a human equivalent of which is (10 mg x .081) x 70 kg = 57 mg.
- Per Human relevance of rodent sulforaphane studies, that’s above a tolerable oral dose of ≈ 50 mg in one serving.
- I didn’t have a problem with eating half that twice a day via microwaved broccoli sprouts from Week 6 through Week 56.
I’d like to know more about how subjects’ memories of adverse events were retained, and subsequently affected their biology and behavior. Pretty sure limbic structures like the hypothalamus as well as lower brain structures played a part.
A 2022 review summarized what was known up to that time regarding Nrf2 and depression:
“Sulforaphane, an organosulfur compound isolated from Brassicaceae plants, is a potent natural NRF2 activator. Sulforaphane:
- Exerts antidepressant- and anxiolytic-like activities and inhibits HPA axis and inflammatory response.
- Has both therapeutic and prophylactic effects on inflammation-related depression.
- Confers stress resilience.
- Protects neurons via autophagy and promotes mitochondrial biogenesis by activating Nrf2.”
https://www.sciencedirect.com/science/article/pii/S2213231722002944 “Nrf2: An all-rounder in depression”