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Updated: May 9, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Antidepressants attenuate the dexamethasone-induced decrease in viability and proliferation of human neuroblastoma
M Leskiewicz1, D Jantas, M Regulska
1Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
Abstract:
Excessive glucocorticoid levels in depressed patients have been associated with atrophic changes in some brain regions, but only few studies suggest that some antidepressants can interfere with deleterious effect of glucocorticoids on neuronal cells. The aim of the present study was to examine the effect of dexamethasone (DEX), a synthetic glucocorticoid and some antidepressants from different chemical groups (imipramine, desipramine, amitriptyline, citalopram, fluoxetine, reboxetine and tianeptine) on SH-SY5Y cells cultured in the medium containing steroid-free serum. DEX in concentrations from 1 to 100 μM did not change LDH release but exposure to 10 μM and 100 μM DEX for 24, 48 and 72 h caused a significant reduction in cell viability and proliferation as confirmed by MTT reduction and BrdU ELISA assays, respectively. Twenty four-hour incubation of cells with antidepressants (0.05-10 μM) and DEX (10 μM) showed that imipramine, amitriptyline, desipramine, citalopram and fluoxetine at concentrations from 0.1 up to 1 μM, reboxetine (0.1 μM) and tianeptine (0.05 μM) prevented the DEX-induced decreases in cell viability and proliferation rate. The protective effects of antidepressants were ameliorated by inhibitors of MAPK/ERK1/2, but not PI3-K/Akt pathway as shown for imipramine, fluoxetine and reboxetine. Moreover, Western blot analysis showed the decrease in the activated form of ERK1/2 (p-ERK) after DEX treatment and this effect was inhibited by imipramine. Thus, the reduction in SH-SY5Y cell viability caused by DEX appears to be related to its antiproliferative activity and some antidepressant drugs in low concentrations attenuate this effect by mechanism which involves the activation of MAPK/ERK1/2 pathway.
Insights
High glucocorticoid levels harm neuronal cells, but some antidepressants protect against this damage. This study found that certain antidepressants, like imipramine and fluoxetine, can prevent dexamethasone-induced cell death by activating the MAPK/ERK1/2 pathway.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Elevated glucocorticoid levels in depression are linked to brain atrophy.
- Antidepressants may counteract the detrimental effects of glucocorticoids on neurons.
Purpose of the Study:
- To investigate the impact of dexamethasone (DEX) and various antidepressants on SH-SY5Y cell viability and proliferation.
- To explore the underlying molecular mechanisms, particularly the involvement of MAPK/ERK1/2 and PI3-K/Akt pathways.
Main Methods:
- SH-SY5Y cells were treated with dexamethasone (DEX) and different antidepressants (imipramine, desipramine, amitriptyline, citalopram, fluoxetine, reboxetine, tianeptine).
- Cell viability and proliferation were assessed using MTT reduction and BrdU ELISA assays.
- Western blot analysis was used to examine the activation of MAPK/ERK1/2 (p-ERK) and PI3-K/Akt pathways.
Main Results:
- Dexamethasone (10-100 μM) significantly reduced SH-SY5Y cell viability and proliferation.
- Several antidepressants, including imipramine, amitriptyline, and fluoxetine, protected cells from DEX-induced toxicity at low concentrations.
- Protective effects were associated with the activation of the MAPK/ERK1/2 pathway, but not PI3-K/Akt.
Conclusions:
- Dexamethasone reduces neuronal cell viability and proliferation via antiproliferative activity.
- Certain antidepressants exhibit neuroprotective effects against glucocorticoid-induced damage.
- The mechanism of protection involves the activation of the MAPK/ERK1/2 signaling pathway.
