title: Tianeptine induces mTORC1 activation in rat hippocampal neurons under toxic conditions.
abstract: Recent studies have demonstrated that mTORC1 activation may be related to antidepressant action. However, the relationship between mTORC1 signaling activation and currently prescribed antidepressants remains unclear.
  
  
  
  The aim of the present study was to determine whether alterations in mTORC1 signaling are observable following treatment with tianeptine under toxic conditions induced by B27 deprivation. Additionally, we investigated whether this drug affects synaptic proteins, neurite outgrowth, and spine density via mTORC1 signaling.
  
  
  
  Using Western blotting, we measured the phosphorylation levels of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK in rat primary hippocampal neurons. Changes in BDNF, dendritic outgrowth, spine density, and synaptic proteins (PSD-95, synaptophysin, and GluR1) were measured.
  
  
  
  Tianeptine significantly increased the phosphorylation of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK. The increase in mTOR phosphorylation was blocked by the PI3K, MEK, and mTORC1 inhibitors. Tianeptine increased BDNF, dendritic outgrowth, spine density, and synaptic proteins; all of these effects were blocked by the mTORC1 inhibitor.
  
  
  
  In this study, we demonstrated that tianeptine activates the mTORC1 signaling pathway and increases dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons.
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Seo
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Hye Yeon
authors.initials: HY
authors.lastname: Cho
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Chan Hong
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.|Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Mansur
authors.affiliation: Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea.
authors.forename: Gyung-Mee
authors.initials: GM
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Woo
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. iybihwc@naver.com.|Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada. iybihwc@naver.com.|Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea. iybihwc@naver.com.|Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea. iybihwc@naver.com.|Department of Psychiatry, Inje University Haeundae Paik Hospital, 1435, Jwa-dong, Haeundae-gu, Busan, 612-030, Republic of Korea. iybihwc@naver.com.
authors.forename: Jung Goo
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. neuro109@hanmail.net.|Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea. neuro109@hanmail.net.|Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea. neuro109@hanmail.net.|Department of Psychiatry, Inje University Haeundae Paik Hospital, 1435, Jwa-dong, Haeundae-gu, Busan, 612-030, Republic of Korea. neuro109@hanmail.net.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000076222:Mechanistic Target of Rapamycin Complex 1; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D016708:Synaptophysin; D058570:TOR Serine-Threonine Kinases; D013841:Thiazepines; C050504:tianeptine; C546842:MTOR protein, human
keywords: Antidepressant drugs; Neuroplasticity; Tianeptine; Toxic conditions; mTORC1 signaling