N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

Ding, Juan; Zhang, Chun; Zhang, Yiwei; Ma, Quanrui; Liu, Yinming; Sun, Tongwen; Liu, Juan

doi:10.4103/1673-5374.262597

Cited by 3 publications

(2 citation statements)

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“…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.…”

Section: Discussionmentioning

confidence: 73%

“…Thus, the subchronic model of SZ was utilized in this study. Moreover, the dose of MK-801 (0.6 mg/kg/day) was utilized in our previous research (Huang et al, 2018;Ding et al, 2019). Based on the hypothesis of this past study, we evaluated the effects of GPER1 deficiency on the hyperlocomotion, stereotypical behaviors, novel object recognition, social interaction, general activity, spatial learning, and the executive capability of the mouse subchronic model of SZ.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2020

Front. Behav. Neurosci.

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The role of estrogen receptors in neuroprotection and cognition has been extensively studied in humans over the past 20 years. Recently, studies have shifted their focus to the use of selective estrogen receptor modulators in the treatment of mental illnesses in the central nervous system. We conducted this study to test the behavioral changes shown by G protein-coupled estrogen receptor 1 knockout (GPER1 KO) and wild-type (WT) mice with MK-801-induced schizophrenia (SZ). GPER1 KO and WT mice received intraperitoneal injections of MK-801 for 14 continuous days. Behavioral, learning and memory, and social interaction changes were evaluated by using the IntelliCage system, open-field, three-chamber social interaction, and novel object recognition tests (NORT). The protein expression levels of the NR2B/CaMKII/CREB signaling pathway were tested via Western blot analysis. The KO SZ group was more likely to show impaired long-term learning and memory function than the WT SZ group. Learning and memory functions were also impaired in the KO Con group. MK-801 administration to the GPER1-KO and WT groups resulted in memory deficiencies and declining learning capabilities. GPER1 deficiency downregulated the expression levels of proteins related to the NR2B/CaMKII/CREB signaling pathway. Our study suggested that GPER1 played an important role in cognitive, learning, and memory functions in the MK-801-induced mouse model of SZ. The mechanism of this role might partially involve the downregulation of the proteins related to the NR2B/CaMKII/CREB signaling pathway. Further studies should focus on the effect of GPER1 on the pathogenesis of SZ in vivo and in vitro.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2020

Front. Behav. Neurosci.

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G protein-coupled estrogen receptor 1 deficiency impairs adult hippocampal neurogenesis in mice with schizophrenia

Zhang¹,

Niu²,

Kong³

et al. 2023

Journal of Chemical Neuroanatomy

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Clozapine Increases Nestin Concentration in the Adult Male Rat Hippocampus: A Preliminary Study

Kayır

Jenkins

Alural

et al. 2022

IJMS

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Patients with schizophrenia, and rodent models of the disease, both exhibit suppressed neurogenesis, with antipsychotics possibly enhancing neurogenesis in pre-clinical models. Nestin, a cytoskeletal protein, is implicated in neuronal differentiation and adult neurogenesis. We hypothesized that schizophrenia pathogenesis involves nestin downregulation; however, few studies have related nestin to schizophrenia. We assessed nestin protein concentration, prepulse inhibition (PPI), and social interaction in the MK-801 model of schizophrenia, with or without antipsychotic (clozapine) treatment. Adult male Sprague–Dawley rats were intraperitoneally administered saline or MK-801 (0.1 mg/kg) to produce a schizophrenia-like phenotype, with concomitant subcutaneous injections of vehicle or clozapine (5 mg/kg). PPI was assessed on days 1, 8, and 15, and social interaction was assessed on day 4. Hippocampus tissue samples were dissected for Western blotting of nestin concentration. MK-801 alone did not alter nestin concentration, while clozapine alone enhanced hippocampal nestin concentration; this effect was not apparent in animals with MK-801 and clozapine co-administration. MK-801 also produced schizophrenia-like PPI disruptions, some of which were reversed by clozapine. Social interaction deficits were not detected in this model. This is the first report of clozapine-induced enhancements of hippocampal nestin concentration that might be mediated by NMDA receptors. Future studies will explore the impact of neurodevelopmental nestin concentration on symptom onset and antipsychotic treatment.

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N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

Cited by 3 publications

References 42 publications

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

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

G protein-coupled estrogen receptor 1 deficiency impairs adult hippocampal neurogenesis in mice with schizophrenia

Clozapine Increases Nestin Concentration in the Adult Male Rat Hippocampus: A Preliminary Study

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