G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice
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 conduc...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00157/full |
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| author | Chun Zhang Chun Zhang Qiang Liu Chun-Yang Yu Feng Wang Yu Shao Kui-Sheng Sun Tao Sun Juan Liu Juan Liu |
| author_facet | Chun Zhang Chun Zhang Qiang Liu Chun-Yang Yu Feng Wang Yu Shao Kui-Sheng Sun Tao Sun Juan Liu Juan Liu |
| author_sort | Chun Zhang |
| collection | DOAJ |
| description | 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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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-13T13:39:20Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-59eddbb3424242b4bee84052fe61f9f42022-12-21T23:43:38ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532020-11-011410.3389/fnbeh.2020.00157553629G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in MiceChun Zhang0Chun Zhang1Qiang Liu2Chun-Yang Yu3Feng Wang4Yu Shao5Kui-Sheng Sun6Tao Sun7Juan Liu8Juan Liu9Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaInstitute of Basic Medical Sciences, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaInstitute of Basic Medical Sciences, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaInstitute of Basic Medical Sciences, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00157/fullschizophreniaMK-801behavioral changeintellicagelearning and memory capacity |
| spellingShingle | Chun Zhang Chun Zhang Qiang Liu Chun-Yang Yu Feng Wang Yu Shao Kui-Sheng Sun Tao Sun Juan Liu Juan Liu G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice Frontiers in Behavioral Neuroscience schizophrenia MK-801 behavioral change intellicage learning and memory capacity |
| title | G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
| title_full | G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
| title_fullStr | G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
| title_full_unstemmed | G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
| title_short | G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
| title_sort | g protein coupled estrogen receptor 1 knockout deteriorates mk 801 induced learning and memory impairment in mice |
| topic | schizophrenia MK-801 behavioral change intellicage learning and memory capacity |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00157/full |
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