PS204. Food-derived antidepressant-like compound ergothioneine promotes neuronal differentiation via activating mTORC1 and neurotrophic factor signaling in neural stem cells.

s | 75 mass index and insulin resistance measures in bipolar disorder and schizophrenia. Bipolar Disord, 2015. 17(5): p. 528–35. PS204 Food-derived antidepressant-like compound ergothioneine promotes neuronal differentiation via activating mTORC1 and neurotrophic factor signaling in neural stem cells. Takahiro Ishimoto, Yukio Kato, Yusuke Masuo, Noritaka Nakamichi Kanazawa University, Japan Abstract Clinically used antidepressants have various side effects, and it would be desirable to develop those with minimal side effects. Ergothioneine (ERGO) is a hydrophilic amino acid and abundantly contained in certain foods. Recently, we have reported that ERGO exhibits antidepressant activity after its oral intake and promotes neuronal differentiation in cultured neural stem cells (NSCs) in mice. However, the mechanism underlying the promotion of neuronal differentiation by ERGO has been minimally clarified. The purpose of the present study is to clarify the detailed mechanism to find a novel target for treatment and/ or prevention of depression. Especially, we focused on mammalian target of rapamycin complex 1 (mTORC1) signaling known as an amino acids sensor. Exposure of cultured NSCs to ERGO significantly increased phosphorylation of mTOR and p70S6K, which are the downstream positive effectors of the mTORC1 signaling, and decreased that of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), which is the downstream negative effector of the mTORC1 signaling. On the other hand, the mTORC1 inhibitor rapamycin significantly suppressed the phosphorylation of mTOR and p70S6K by ERGO. Moreover, ERGO significantly increased expression of mRNA and gene product of neurotrophin5 (NT5), and the number of neuronal marker βIIItubulin positive cells. Furthermore, rapamycin or an inhibitor of tropomyosin receptor kinase B (TrkB), which is a receptor for NT5, significantly suppressed the increase in βIII-tubulin positive cells by ERGO. These results suggest that ERGO may promote neuronal differentiation via activation of mTORC1 and NT5/TrkB signaling in NSCs. ERGO or its derivatives could be a possible candidate for treatment and/or prevention of certain neuropsychiatric diseases including depression because defects in mTORC1 and NT5/TrkB signaling are related with deterioration and/or onset of them.Clinically used antidepressants have various side effects, and it would be desirable to develop those with minimal side effects. Ergothioneine (ERGO) is a hydrophilic amino acid and abundantly contained in certain foods. Recently, we have reported that ERGO exhibits antidepressant activity after its oral intake and promotes neuronal differentiation in cultured neural stem cells (NSCs) in mice. However, the mechanism underlying the promotion of neuronal differentiation by ERGO has been minimally clarified. The purpose of the present study is to clarify the detailed mechanism to find a novel target for treatment and/ or prevention of depression. Especially, we focused on mammalian target of rapamycin complex 1 (mTORC1) signaling known as an amino acids sensor. Exposure of cultured NSCs to ERGO significantly increased phosphorylation of mTOR and p70S6K, which are the downstream positive effectors of the mTORC1 signaling, and decreased that of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), which is the downstream negative effector of the mTORC1 signaling. On the other hand, the mTORC1 inhibitor rapamycin significantly suppressed the phosphorylation of mTOR and p70S6K by ERGO. Moreover, ERGO significantly increased expression of mRNA and gene product of neurotrophin5 (NT5), and the number of neuronal marker βIIItubulin positive cells. Furthermore, rapamycin or an inhibitor of tropomyosin receptor kinase B (TrkB), which is a receptor for NT5, significantly suppressed the increase in βIII-tubulin positive cells by ERGO. These results suggest that ERGO may promote neuronal differentiation via activation of mTORC1 and NT5/TrkB signaling in NSCs. ERGO or its derivatives could be a possible candidate for treatment and/or prevention of certain neuropsychiatric diseases including depression because defects in mTORC1 and NT5/TrkB signaling are related with deterioration and/or onset of them. PS205 Innate immune molecules activate microglia in mPFC to induce neuronal and emotional changes in mice. Shiho Kitaoka1, Tomoyuki Furuyashiki1, Yuki Imoto2, Kazuki Nakayama1, Shuh Narumiya2, Xiang Nie1, Atsubumi Ogawa2, Eri Segi-Nishida3, Kohei Tanaka2, Ayaka Tomohiro1 1Kobe University, Japan, 2Kyoto University, Japan, 3Tokyo University of