Tianeptine induces mTORC1 activation in rat hippocampal neurons under toxic conditions.
RATIONALE
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Seo|Mi Kyoung|MK|', 'McIntyre|Roger S|RS|', 'Cho|Hye Yeon|HY|', 'Lee|Chan Hong|CH|', 'Park|Sung Woo|SW|', 'Mansur|Rodrigo B|RB|', 'Kim|Gyung-Mee|GM|', 'Baek|Jun Hyung|JH|', 'Woo|Young Sup|YS|', 'Lee|Jung Goo|JG|', 'Kim|Young Hoon|YH|']
D000818:Animals D000929:Antidepressive Agents, Tricyclic D003712:Dendrites D004195:Disease Models, Animal D006624:Hippocampus D000076222:Mechanistic Target of Rapamycin Complex 1 D016501:Neurites D009474:Neurons D019869:Phosphatidylinositol 3-Kinases D010766:Phosphorylation D051381:Rats D038762:Ribosomal Protein S6 Kinases, 70-kDa D015398:Signal Transduction D013569:Synapses D016708:Synaptophysin D058570:TOR Serine-Threonine Kinases D013841:Thiazepines
Tianeptine Toxic conditions mTORC1 signaling Antidepressant drugs Neuroplasticity