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41 In detail, the elevated extracellular ATP induced by SD stress stimulates P2 7 R and down-regulates the expression of 5-HT 2B R by suppressing the activation of AKT, which inhibits the phosphorylation of FoxO3a and promotes its transportation into the nucleus, the reduced 5-HT 2B R alleviates the inhibition of STAT3 to cPLA 2 , the activated cPLA 2 further increases the release of AA and PGE2, these indicators have high relationship with the depressive-like behaviors, because in P2X 7 R knockout mice, the above changes of these indicators and behavioral performance are all eliminated

Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways