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

Zhang, Chun; Liu, Qiang; Yu, Chunyang; Wang, Feng; Shao, Yu; Sun, Kuisheng; Sun, Tongwen; Liu, Juan

doi:10.3389/fnbeh.2020.00157

Cited by 8 publications

(5 citation statements)

References 49 publications

(56 reference statements)

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“…Furthermore, we explored the NMDA-CaMKII signal pathway which is upstream of nNOS. As a downstream signal factor of the NMDAR subunit, CaMKII is an extremely abundant protein kinase in brain tissue that participates in a variety of signaling cascade reactions and is an important mediation center for the regulation of learning and memory ( Zhang C. et al, 2020 ). CaMKII has been shown to reposition within the NMDAR complex in response to non-ionotropic NMDAR signaling ( Aow et al, 2015 ; Stein et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Yin

Qian

Chen

et al. 2021

Front. Behav. Neurosci.

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Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Yin

Qian

Chen

et al. 2021

Front. Behav. Neurosci.

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“…GPER has been associated with several physiological functions, such as angiogenesis, brain development, and homeostasis [28,101], but it also participates in several pathological processes, such as carcinogenesis and metastasis development [74][75][76]. Although GPER improves the correct development of neuronal, connective, and epithelial tissues [35,36], changes in its expression can deregulate homeostasis and trigger malignant development [31]. GPER expression levels depend on the cancer type, which could serve as a prognosis marker for the tissue affected [49][50][51].…”

Section: Discussionmentioning

confidence: 99%

“…Also, the Gβγ subunit could transactivate the epidermal growth factor receptor (EGFR) via heparin-binding EGF-like growth factor (HB-EGF) activating the phosphatidylinositol 3-kinase (PI3K) and MAPK pathways (Figure 2) [30,31]. Furthermore, these mechanisms have been associated with the proliferation of non-tumorigenic breast cells MCF10A ex vivo [32], dendritic spin density related to spatial learning and memory [33][34][35], and glucose and lipid homeostasis [36].…”

Section: Gper/gpr30 Signaling In Normal Tissuesmentioning

confidence: 99%

GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments

Tirado-Garibay,

Falcón-Ruiz,

Ochoa-Zarzosa

et al. 2023

IJMS

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Estrogens and their role in cancer are well-studied, and some cancer types are classified in terms of their response to them. In recent years, a G protein-coupled estrogen receptor (GPER) has been described with relevance in cancer. GPER is a pleiotropic receptor with tissue-specific activity; in normal tissues, its activation is related to correct development and homeostasis, while in cancer cells, it can be pro- or anti-tumorigenic. Also, GPER replaces estrogen responsiveness in estrogen receptor alpha (ERα)-lacking cancer cell lines. One of the most outstanding activities of GPER is its role in epithelial–mesenchymal transition (EMT), which is relevant for metastasis development. In addition, the presence of this receptor in tumor microenvironment cells contributes to the phenotypic plasticity required for the dissemination and maintenance of tumors. These characteristics suggest that GPER could be a promising therapeutic target for regulating cancer development. This review focuses on the role of GPER in EMT in tumorigenic and associated cells, highlighting its role in relation to the main hallmarks of cancer and possible therapeutic options.

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“…Therefore, it is reasonable to find increased expression of pro-apoptotic protein marker-Bax, and decreased expression of anti-apoptotic protein-tyrosine hydroxylase in the brains of MK-801-treated mice. The brain regions we tested included prefrontal cortex and hippocampus, which are believed to be important for the onset and/or development of SCZ ( 33 ). In fact, clinical data indicated that the loss of neurons in brains of SCZ patients, especially in the prefrontal cortex, was the basis of many core symptoms of SCZ and was closely related to the prognosis of the disease ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin Rescued MK-801-Induced Schizophrenia–Like Behaviors in Mice via Oxidative Stress Pathway

2022

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Schizophrenia (SCZ) affects approximately 1% population worldwide, and the first-line antipsychotics have partial reactivity or non-reactivity with side effects. Therefore, there is an urgent need to find more effective drugs. Paeoniflorin (PF) is the main effective component of traditional Chinese medicine from white peony, red peony and peony bark, which acts as a neuroprotective agent. The purpose of this study was to investigate whether PF can rescue MK-801 induced schizophrenia-like behavior in mice. Our results demonstrated that intragastric administration of PF ameliorated MK-801 induced schizophrenia–like behaviors in mice as demonstrated by prepulse inhibition of acoustic startle response, fear conditioning test for memory and open field test for activity. In contrast, the first-line antipsychotics-olanzapine reversed the prepulse inhibition deficits and hyperactivities, but not memory deficits, in the model mice. Further analysis showed that PF reduced oxidative stress in the MK-801-treated mice, as evidenced by the increased superoxide dismutase levels and decreased malondialdehyde levels in the blood of the model mice. In addition, PF treatment inhibited the expression of the apoptotic protein Bax and restored the expression of tyrosine hydroxylase in the brains of the model mice. in vitro data indicated that PF protected against oxidative stress induced neurotoxicity in the primary cultured hippocampal neurons. In conclusion, our results were the first to provide evidence that PF rescued schizophrenia-like behaviors (both positive symptoms and cognitive impairments) in rodents through oxidative stress pathway, and therefore provide a novel strategy for treatment of SCZ. However, more pre-clinical and clinical research are needed to translate the present findings into clinics for a treatment of schizophrenia.

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

Cited by 8 publications

References 49 publications

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus

GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments

Paeoniflorin Rescued MK-801-Induced Schizophrenia–Like Behaviors in Mice via Oxidative Stress Pathway

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