Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK-801.

The purpose of the present study was to investigate effects of N-methyl-D-aspartate (NMDA) on proliferation and apoptosis of hippocampal neural stem cells (NSCs) treated with dizocilpine (MK-801). Cultures of hippocampal NSCs were randomly divided into four groups consisting of an untreated control, cells treated with MK-801, NMDA and a combination of MK801 and NMDA (M+N). Proliferative and apoptotic responses for each of the experimental groups were determined by MTS and flow cytometry. The results revealed that MK-801 and NMDA exerted significant effects on hippocampal NSCs proliferation. Cell survival rates decreased in MK-801, NMDA and M+N treated groups compared with the control group. Cells survival rates in NMDA and M+N treated groups increased compared with the MK-801 treated group. MK-801 and NMDA were demonstrated to significantly affect apoptosis in hippocampal NSCs. Total and early stages of apoptosis in MK-801 and NMDA groups significantly increased compared with the control group. Total and early apoptosis of NSCs in the M+N group significantly decreased compared with MK-801 and NMDA groups. Late apoptosis of NSCs in MK-801 and NMDA groups significantly decreased compared with the control group. Late apoptosis of NSCs in the M+N group significantly increased compared with MK-801 and NMDA groups. The present study revealed that MK-801 inhibited proliferation and increased apoptosis in hippocampal NSCs. NMDA may reduce the neurotoxicity induced by MK-801, which may be associated with its activity towards NMDA receptors and may describe a novel therapeutic target for the treatment of schizophrenia.