The effect of lansoprazole on MK-801-induced schizophrenia-like behaviors in mice

Bae, Hyo Jeoung; Bae, Ho Jung; Kim, Jae Youn; Park, Keontae; Yang, Xingquan; Park, Se Jin; Kim, Dong Hyun; Shin, Chan Young; Ryu, Jong Hoon

doi:10.1016/j.pnpbp.2022.110646

Cited by 8 publications

(5 citation statements)

References 66 publications

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“…The major role of TNF-α in the pathophysiology of schizophrenia at various stages has been reported several times in previous studies, including in animal models [37][38][39]. Our study is consistent with previous ndings that serum TNF-α levels were elevated in patients with CMS, suggesting a relationship between neuroin ammation and schizophrenia.…”

Section: Discussionsupporting

confidence: 93%

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

Yang,

Peng,

Yang

et al. 2024

Preprint

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Background: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. Methods: The study enrolled 31 TRS and 49 CMS male patients, and 53 healthy controls. Serum MMP-2 and TNF-a levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. Results: Serum TNF-a and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F=4.289, P=0.016; F=4.682, P=0.011, respectively). Bonferroni correction demonstrated that serum TNF-a levels were significantly elevated in CMS patients (P=0.022) and MMP-2 levels were significantly higher in TRS patients (P=0.014) compared to healthy controls. In TRS patients, TNF-a was negatively correlated with age (r=-0.435, P=0.015) and age of onset (r=-0.409, P=0.022). In CMS patients, MMP-2 and TNF-a were negatively correlated with PANSS negative and total scores, and TNF-a was negatively correlated with PANSS general psychopathology scores (all P<0.05). MMP-2 levels were positively correlated with TNF-a levels (P<0.05), but not with cognitive function (P>0.05). Conclusion: The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

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Section: Discussionsupporting

confidence: 93%

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

Yang,

Peng,

Yang

et al. 2024

Preprint

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“…Interestingly, D-pinitol can exhibit anti-inflammatory and anti-cancer activities through the NF-kB signaling pathway and reduce the synthesis of pro-inflammatory cytokines (Sethi et al, 2008) et al, 2010). In the current study, we confirmed that MK-801 treatment increased pro-inflammatory cytokines including TNF-α and IL-6, as reported by others (Bae et al, 2023). Thus, activation of the NF-kB signaling pathway and increased pro-inflammatory cytokines in the prefrontal cortex might be associated with MK-801-induced schizophrenia-like behavior (Murphy et al, 2021).…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, we found that D‐pinitol normalized increases of pNF‐kB and pro‐inflammatory cytokines induced by MK‐801 in the prefrontal cortex. However, we did not observe any changes in such cytokines in the hippocampus (Figure S1), as shown in our previous report (Bae et al, 2023). Therefore, the normalization of enhanced NF‐kB signaling pathway and consequent increase in pro‐inflammatory cytokines in the cortex may be associated with the effect of D‐pinitol against schizophrenia‐like behavior induced by NMDA receptor antagonist.…”

Section: Discussionsupporting

confidence: 89%

“…Fortunately, D‐pinitol did not show any motor dysfunction, one of severe adverse effects of conventional antipsychotics. However, aripiprazole still impaired fine motor coordination measured by balance beam test, as observed previously (Bae et al, 2023). Therefore, D‐pinitol would be a potential antipsychotic candidate without any adverse effects such as movement disorders.…”

Section: Discussionsupporting

confidence: 86%

“…The balance beam test is useful for detecting fine movement deficits in balance and motor coordination (Luong et al, 2011). Previously, we have reported that aripiprazole can cause fine motor coordination deficits (Bae et al, 2023), probably, due to its partial agonism of dopamine D2 receptor (Kikuchi et al, 2021). Similarly, haloperidol can cause severe cataleptic behavior (Jeong et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

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Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Kim,

Kong,

Kim

et al. 2023

Phytotherapy Research

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Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D‐pinitol could ameliorate schizophrenia‐like behaviors induced by MK‐801, an N‐methyl‐D‐aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D‐pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D‐pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D‐pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D‐pinitol. Single administration of D‐pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D‐Pinitol also reversed social behavior deficits and cognitive impairments induced by MK‐801 without causing any motor coordination deficits. Furthermore, D‐pinitol reversed increased expression levels of pNF‐kB induced by MK‐801 treatment and consequently increased expression levels of TNF‐α and IL‐6 in the prefrontal cortex. These results suggest that D‐pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down‐regulating transcription factor NF‐κB and pro‐inflammatory cytokines in the prefrontal cortex.

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Behavioral and transcriptional effects of repeated electroconvulsive seizures in the neonatal MK-801-treated rat model of schizophrenia

Lee,

Huh,

Park

et al. 2023

Psychopharmacology

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The effect of lansoprazole on MK-801-induced schizophrenia-like behaviors in mice

Cited by 8 publications

References 66 publications

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Behavioral and transcriptional effects of repeated electroconvulsive seizures in the neonatal MK-801-treated rat model of schizophrenia

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