title: Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice.
abstract: Clinically 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.
  
  
  
  To 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.
  
  
  
  Diet 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.
  
  
  
  Thus, 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.
authors.affiliation: Faculty of Pharmacy Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Nakamichi
authors.affiliation: Faculty of Pharmacy Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Faculty of Pharmacy Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Faculty of Pharmacy Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Masuo
authors.affiliation: School of Medicine Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Wakayama
authors.affiliation: Life Science Institute Co. Ltd.2-6-6 Nihombashi-Horidomecho Chuo-ku Tokyo 103-0012 Japan; L•S Corporation Co. Ltd.3-10-1 Ningyocho-Nihonbashi Chuo-ku Tokyo 103-0013 Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: Life Science Institute Co. Ltd.2-6-6 Nihombashi-Horidomecho Chuo-ku Tokyo 103-0012 Japan; L•S Corporation Co. Ltd.3-10-1 Ningyocho-Nihonbashi Chuo-ku Tokyo 103-0013 Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Sutoh
authors.affiliation: Life Science Institute Co. Ltd. 2-6-6 Nihombashi-Horidomecho Chuo-ku Tokyo 103-0012 Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Usumi
authors.affiliation: School of Medicine Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Iseki
authors.affiliation: Faculty of Pharmacy Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University Kanazawa 920-1192 Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000178:diet therapy / Q000188:drug therapy; D004880:Ergothioneine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D020076:Pleurotus
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D010936:Plant Extracts; D004880:Ergothioneine
keywords: Antidepressant effect; OCTN1; depression; disposition; ergothioneine; neuronal differentiation