Down-regulation of N-methyl-D-aspartate receptor subunits 1 affects neurogenesis of hippocampal neural stem cells

[摘要] Schizophrenia is a common and serious mental illness characterized by severe impairments in thinking, emotions, and behaviors. Usually, the cognitive deficits of schizophrenia are closely associated with abnormal neurogenesis due to the hypofunction of certain neural receptors such as N-methyl-D-aspartate receptors (NMDARs), which mediates neurotransmission. However, little is known about the involvement of NMDAR1 in regulating hippocampal neurogenesis in schizophrenia. In the current study, we present evidence suggesting that NMDAR1 regulates hippocampal neurogenesis as lentivirus-mediated shRNA silencing NMDAR1 gene or blocking with MK-801 results in abnormal neurogenesis consistently found in schizophrenia. The important finding was clearly demonstrated by the multiparametric assessments, including morphology, immunofluorescence, western blotting, and flow cytometry. Simultaneously, our results indicated that knockdown and blockade of NMDAR1 significantly attenuated the proliferation of hippocampal neural stem cells (hNSCs) and decreased the differentiation to neurons. More importantly, the blockade of NMDAR1 with MK-801 aggravated the apoptosis of hNSCs. Thus, it is likely that NMDAR1 functions as a new target for the treatment of schizophrenia. Our present study may provide a novel insight for further investigation of the pathogenesis of schizophrenia.

[学科分类] 仪器

[关键词] Schizophrenia;RNAi;MK-801;NMDAR1;Hippocampal neural stem cells