Expression of NR1 and apoptosis levels in the hippocampal cells of mice treated with MK-801

Abstract

The aim of the present study was to investigate the characteristics of N‑methyl‑D‑aspartate receptor R1 (NR1) expression and apoptosis in the nerve cells of the hippocampus in schizophrenia‑like mice. C57BL/6 mice were randomly allocated to the following groups: i) Blank group; ii) MK‑801 group; iii) MK‑801+NMDA group, according to body weight. The NMDAR antagonist, MK‑801 (0.6 mg/kg/d) was intraperitoneally injected daily for 14 days to induce a schizophrenia‑like phenotype mouse model, and the effect of the NMDA injection via the lateral ventricle was observed. The results demonstrated that the number of NR1 positive cells in the MK‑801 group increased in the CA1 and DG regions, indicating that NMDA may reverse this change. The level of damage decreased in the MK‑801 treated group when compared with the blank group in the CA3 region. The protein expression of NR1 increased however, at the mRNA expression level, NR1 was lower in the MK‑801 treated group when compared to the blank group; NMDA also reversed this change. In addition, early and total apoptosis detected in the hippocampal nerve cells was significantly increased in the MK‑801 group when compared with the blank group, which was reversible following treatment with NMDA. These results indicated that NMDA may regulate the expression of NR1 and suppress apoptosis in hippocampal nerve cells in schizophrenia‑like mice. Thus, NR1 may be a promising therapeutic target for the treatment of schizophrenia.

G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice

“…Numerous studies have confirmed that NMDAR antagonists induce SZ-related behavior (Jeon et al, 2017). Meanwhile, our previous studies (Ding et al, 2017(Ding et al, , 2019 and other work (Seillier and Giuffrida, 2009;Jacklin et al, 2012;Karamihalev et al, 2014;Li et al, 2016) found cognition impairment and alterations in anatomical and neurochemical aspects in a mouse subchronic model of SZ induced by the intraperitoneal injection of MK-801 for 14 consecutive days. Given that SZ is a chronic psychiatric disorder, subchronic administration with MK-801 might better represent the enduring cognition deficits of SZ (Karamihalev et al, 2014;Xiu et al, 2014), meaning it may serve as a robust model for the disease.…”

SEP‐363856 exerts neuroprotection through the PI3K/AKT/GSK‐3β signaling pathway in a dual‐hit neurodevelopmental model of schizophrenia‐like mice

“…Dysregulation of apoptosis, reduced expression of the antiapoptotic protein Bcl‐2, and an elevated ratio of the proapoptotic protein Bax/Bcl‐2 have all been seen in both clinical investigations and postmortem brain tissue examinations of SZ patients (Jarskog et al, 2004). MK‐801 induced apoptosis of hippocampal cells and downregulation of Bcl‐2 expression in an SZ‐like animal model (Ding et al, 2017). Furthermore, it has been demonstrated that exposure to NDMA receptor antagonists during perinatality results in a persistent disruption of hippocampus apoptosis (Jarskog, 2006; Jevtic et al, 2016; Osacka et al, 2023).…”

Activation of A2Badenosine receptor protects against demyelination in a mouse model of schizophrenia

“…A total of 40 mice were randomly divided into four groups (10 mice per group) as follows: Control group (Control), MK-801 group (MK-801), MK-801 plus A 2B AR agonist group (MK-801 + BAY) and MK-801 plus A 2B AR antagonist group (MK-801 + PSB). The SCZ model was established according to a previously described method (26). Briefly, mice were injected intraperitoneally with MK-801 (0.6 mg/kg/day; cat.…”