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Tianeptine induces mTORC1 activation in rat hippocampal neurons under toxic conditions
Mi Kyoung Seo1, Roger S McIntyre2,3, Hye Yeon Cho1
1Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
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.
Insights
Tianeptine activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. This activation promotes neuronal growth and synaptic protein expression in hippocampal neurons under toxic conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Emerging evidence links mechanistic target of rapamycin complex 1 (mTORC1) activation to antidepressant effects.
- The precise relationship between mTORC1 signaling and established antidepressant medications is not fully understood.
Purpose of the Study:
- To investigate if tianeptine alters mTORC1 signaling in rat hippocampal neurons subjected to B27 deprivation.
- To determine if tianeptine influences synaptic proteins, neurite outgrowth, and spine density via mTORC1 signaling.
Main Methods:
- Western blotting was employed to quantify phosphorylation levels of key proteins including mTORC1, 4E-BP-1, p70S6K, Akt, and ERK in primary rat hippocampal neurons.
- Measurements of brain-derived neurotrophic factor (BDNF), dendritic outgrowth, spine density, and synaptic proteins (PSD-95, synaptophysin, GluR1) were conducted.
Main Results:
- Tianeptine treatment significantly elevated the phosphorylation of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK.
- Inhibitors of PI3K, MEK, and mTORC1 blocked the observed increase in mTOR phosphorylation.
- Tianeptine enhanced BDNF levels, dendritic outgrowth, spine density, and synaptic protein expression, effects which were abrogated by an mTORC1 inhibitor.
Conclusions:
- Tianeptine activates the mTORC1 signaling pathway in rat hippocampal neurons under toxic conditions.
- The observed increases in dendritic outgrowth, spine density, and synaptic proteins are mediated by mTORC1 signaling following tianeptine treatment.
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