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

Abstract

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.

Social withdrawal and anxiety-like behavior have an impact on zebrafish adult neurogenesis

“…More specifically, regarding the dorsal telencephalon, the densities of mitotically active cells were decreased in the proliferation zones of Dm and Dld, two putative homolog structures of basolateral amygdala (BLA) and hippocampus of mammals ( O'Connell and Hofmann, 2011 ), regulating both social behavior ( Bickart et al, 2014 ; FeldmanHall et al, 2021 ) as well as fear and anxiety-like responses ( Lal et al, 2018 ; Ghasemi et al, 2022 ). Our results further support previous evidence on decreased hippocampal NSPCs proliferation by NMDAR hypofunction ( Maeda et al, 2007 ; Song et al, 2016 ; Ding et al, 2018 ). Moreover, in rodent animal models, chronic stress or deficits in social communication are characterized by the dysregulation of different stages in postnatal hippocampal neurogenesis including neural progenitor proliferation and differentiation ( Malberg and Duman, 2003 ; Heine et al, 2004 ; Hong et al, 2019 ; Gioia et al, 2022 ).…”

Reversible Changes in BDNF Expression in MK-801-Induced Hippocampal Astrocytes Through NMDAR/PI3K/ERK Signaling

“…In addition, MK801 for as little as 24 h enhanced astrocyte viability, as measured by MMT assay. Ding et al (2018) found that neural stem cell proliferation and viability were significantly reduced by MK-801 treatment for 24 h, but the concentration of MK-801 was high enough (200 µM) to induce significant apoptosis (Ding et al, 2018). Consistent with the present results, MK-801 enhanced expression of the astrocyte-specific intermediate filament protein GFAP, a marker of cell activation in response to local brain injury (Yu et al, 2015).…”

Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus

“…Inhibition of NMDAR by MK801 leads to apoptosis of neurons [ 65 , 66 ]. MK-801 also inhibits proliferation and increases apoptosis in hippocampal neural stem cells [ 67 ]. We found that the upregulation of DDIT4 expression in the hippocampus by sevoflurane can be inhibited through the supplementation of NMDA in the hippocampus.…”