The modulating effect of myo-inositol and prototypical antidepressants on markers of cellular resilience in cultured human neuroblastoma cells
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Although several antidepressants are available for the treatment of depression, certain limitations are common, including drug resistance and significant side effects. Recently, several studies indicated the possibility of neurodegeneration in the pathophysiology of depression. Oral myo-inositol (mlns) has been found to be effective in the treatment of depression. It is thought that understanding the mechanism of action of mlns may contribute to the understanding of the pathophysiological basis of depression. The aim of the current study was to determine the possible neuroprotective effects of mlns, in comparison with other prototype or experimental antidepressants, against glutamate-induced excitotoxicity in human neuroblastoma cells. For this purpose, the cells were pretreated for 24 hours with different concentrations of either mlns, one of a series of antidepressants, or a combination of mlns and an antidepressant, all with or without 15 mM glutamate. The MTT cell proliferation assay was employed to determine cell viability, while the comet assay was used to determine DNA fragmentation. After pretreatment with the different regimes it was found that most drugs had no significant effect on cell viability, while 10 mM mlns decreased cell viability. Interestingly, fluoxetine (10 μM) and lithium (2,5 or 10 mM) protect against the mlns-induced neurodegeneration. lmipramine alone (10 μM), imipramine in combination with mlns and 2 mM or 10 mM lithium in combination with mlns caused an increase in glutamate sensitivity, while 0.23 μM gabapentin protected against glutamate-induced excitotoxicity. Data from the comet assay largely supports the data from the MTT cell proliferation assay. In conclusion, mlns is not neuroprotective, but rather neurodegenerative in this in vitro model and results also do not suggest an additive neuroprotective effect of the combination of mlns with other antidepressants. The study provides little support for the neuroprotective hypothesis of antidepressant action.
- ETD@PUK