Abstract
BackgroundClinically used antidepressants suffer from various side effects. Therefore, we searched for a safe antidepressant with minimal side effects among food ingredients that are distributed to the brain. Here, we focused on ERGO (ergothioneine), which is a hydrophilic antioxidant and contained at high levels in edible golden oyster mushrooms. ERGO is a typical substrate of carnitine/organic cation transporter OCTN1/SLC22A4, which is expressed in the brain and neuronal stem cells, although little is known about its permeation through the BBB (blood–brain barrier) or its neurological activity.MethodsTo clarify the exposure of ERGO to brain and the possible antidepressant‐like effect after oral ingestion, ERGO or GOME (golden oyster mushroom extract) which contains 1.2% (w/w) ERGO was mixed with feed and provided to mice for 2 weeks, and then ERGO concentration and antidepressant‐like effect were evaluated by LC‐MS/MS and FST (forced swimming test) or TST (tail suspension test), respectively.ResultsDiet containing ERGO or GOME greatly increased the ERGO concentrations in plasma and brain, and significantly decreased the immobility time in both FST and TST. The required amount of GOME (~37 mg/day) to show the antidepressant‐like effect corresponds to at most 8 g/day in humans. In mice receiving GOME‐containing diet, doublecortin‐positive cells showed a significant increase from the basal level, suggesting promotion of neuronal differentiation.ConclusionThus, orally ingested ERGO is transported across the BBB into the brain, where it may promote neuronal differentiation and alleviate symptoms of depression at plausibly achieved level of daily ingestion.
Highlights
Depression is a mental illness with serious social consequences, and about 20% of the population suffers from the mental illness at some point in their lifetime (Browne and Lucki 2013)
We measured the concentration of ERGO in blood, plasma, brain, liver, and kidney at 2 weeks after the mice had been started on diet containing 0.1–10% GOME (w/w; Fig. 1A)
The decrease in Kp occurred at the plasma ERGO concentration of about 1–2 lg/mL (4–8 lmol/L), which is close to the Michaelis constant (Km) for ERGO of OCTN1 (~5 lmol/L, Kato et al 2010)
Summary
Depression is a mental illness with serious social consequences, and about 20% of the population suffers from the mental illness at some point in their lifetime (Browne and Lucki 2013). Various antidepressant therapeutic agents, including selective serotonin reuptake inhibitors, serotonin–noradrenaline reuptake inhibitors, and tricyclic antidepressants, are currently used for the treatment of depression. These drugs have multiple side effects (Bet et al 2013; Alusik et al 2014). It would obviously be desirable to develop antidepressant drugs with few or no side effects that can be safely used in long-term treatment. From this point of view, a useful strategy might be to search for antidepressant activity among edible products using animal models of depression. Conclusion: orally ingested ERGO is transported across the BBB into the brain, where it may promote neuronal differentiation and alleviate symptoms of depression at plausibly achieved level of daily ingestion
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