Neuroprotective efects of mirtazapine and imipramine and their efect in pro‐ and anti‐apoptotic gene expression in human neuroblastoma cells.

Abstract

Background Experimental and clinical studies indicate that neuronal death with the presence of high levels of reactive oxygen species are present in depressed patients and antidepressants might display neuroprotective efects against them. However, the mechanisms underlying antidepressant neuroprotection are not completely understood. In our previous study, we showed that mirtazapine modulated the expression of pro- and anti-apoptotic proteins in mouse brain structures, but there are no

data in human cells. Thus, this work was designed to study the possible neuroprotective properties of mirtazapine and imi- pramine, two commercially available antidepressants with diferent primary mechanisms of action, in human neuroblastoma

SH-SY5Y cells against an oxidative insult.

Methods SH-SY5Y cells were preincubated with mirtazapine and imipramine (1–20 μM) for 24 h, then hydrogen perox- ide (H2O2) was added into the medium containing the antidepressants for additional 24 h, and MTT assay was carried out

subsequently. Also, to elucidate the molecular mechanism underlying the neuroprotective properties of antidepressants, we

investigated the efects of mirtazapine and imipramine (2 μM) in pro- and anti-apoptotic proteins gene expression in SH- SY5Y cells.

Results Mirtazapine (1 and 2 μM) and imipramine (1and 2 μM) protected against hydrogen peroxide-induced cellular viability impairment. Most importantly, both compounds reduced p53 mRNA expression, but only imipramine enhanced the Bcl-2/Bax ratio. Conclusions The obtained data indicate that mirtazapine and imipramine have neuroprotective efects against H2O2-induced

cell death. Although both antidepressants reduced Bax and p53 mRNA expression, only the protection mediated by imipra- mine might be due to its ability to enhance Bcl-2/Bax ratio.