Noscapine modulates neuronal response to oxygen-glucose deprivation/reperfusion injury via activation of sigma-1 receptor in primary cortical cultures

Abstract

In the present study, we investigated the effects of noscapine (0.5-2 μM), an alkaloid from the opium poppy (Papaver somniferum), on primary murine cortical neurons exposed to 60 min oxygen�glucose deprivation (OGD) in the presence of 5 μM BD-1047, a selective sigma-1 receptor antagonist. The experiments were performed on cortical neurons after 11�16 days of culture. To initiate oxygen�glucose deprivation, the culture medium was transferred to glucosefree DMEM, and placed in a humidified incubation chamber containing a mixture of 95 N2 and 5 CO2 at 37 °C for 60 min. In order to explore the effect on neurons under oxygen�glucose deprivation in this condition, some cultures were pretreated with noscapine and BD1047 together, 24 h prior to OGD followed by 24 h recovery. Cell viability, nitric oxide (NO) production and intracellular calcium concentration (Ca2+i) levels were evaluated by MTT assay, the modified Griess method, and Fura-2, respectively. Pretreatment of the cultures with noscapine in the presence of BD1047 significantly increased cell viability and decreased NO generation in a dosedependent manner compared to BD1047 alone. Pretreatment with 2 μM noscapine and BD-1047 was shown to decrease the rise in Ca2+i induced by sodium azide (NaN3) and glucose deprivation. We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen�glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and Ca2+i levels. © 2020, Iranian Journal of Pharmaceutical Research. All rights reserved