Abstract:

Objective   To investigate protective effects of paliperidone on cortical neurons injured by dizocilpine and associated mechanisms. Methods   Cortical neurons were dissociated from embryonic rats at E15 and cultured in DMEM/F12 medium supplemented with 10% fetal bovine serum. After cortical neurons were injured by dizocilpine, paliperidone at different concentrations was added to detect their protection effects. MTT assay was adopted to detect cell viability. Lactate dehydrogenase (LDH) activity and intracellular Ca2+ concentration were measured with LDH cytotoxic assay kit and laser scanning microscope respectively. Total length and number of neurites were calculated with Image Pro-Plus software. mRNA expressions of Akt1 and GSK3β which associated with neurogenesis and neurodevelopment were detected by realtime PCR. Results   In contrast with control group, cortical neurons in dizocilpine group exhibited apparently reduced viability, increased concentration of intracellular calcium and LDH release (P＜0.01), declined number and total length of neurites (P＜0.01) and decreased expressions of Akt1 and GSK3βat mRNA level detected by RT-PCR assay (P＜0.01). Compared to dizocilpine group, viability of cultured cortical neurons was increased（P＜0.01） and LDH activity was declined due to the addition of paliperidone (P＜0.001). Intracellular Ca2+ concentration in paliperidone group was weaker than that in dizocilpine group (P＜0.01). The length and number of neurites in paliperidone group were greater than those in dizocilpine group (P＜0.01). Real-time PCR also showed that the expressions of Akt1 and GSK3β were higher in paliperidone group than those in dizocilpine group(P＜0.01). Conclusion   Paliperidone can effectively protect cortical neurons from dizocilpine injury, inhibit neuron apoptosis and promote neurogenesis via Akt1-GSK3β signaling pathway.

Key words: Cortical neuron; Paliperidone; Dizocilpine; Protection