Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726131/ https://www.ncbi.nlm.nih.gov/pubmed/33324181 http://dx.doi.org/10.3389/fnbeh.2020.00157 |
_version_ | 1783620819158564864 |
---|---|
author | Zhang, Chun Liu, Qiang Yu, Chun-Yang Wang, Feng Shao, Yu Sun, Kui-Sheng Sun, Tao Liu, Juan |
author_facet | Zhang, Chun Liu, Qiang Yu, Chun-Yang Wang, Feng Shao, Yu Sun, Kui-Sheng Sun, Tao Liu, Juan |
author_sort | Zhang, Chun |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7726131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77261312020-12-14 G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice Zhang, Chun Liu, Qiang Yu, Chun-Yang Wang, Feng Shao, Yu Sun, Kui-Sheng Sun, Tao Liu, Juan Front Behav Neurosci Behavioral Neuroscience 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. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726131/ /pubmed/33324181 http://dx.doi.org/10.3389/fnbeh.2020.00157 Text en Copyright © 2020 Zhang, Liu, Yu, Wang, Shao, Sun, Sun and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Behavioral Neuroscience Zhang, Chun Liu, Qiang Yu, Chun-Yang Wang, Feng Shao, Yu Sun, Kui-Sheng Sun, Tao Liu, Juan G Protein-Coupled Estrogen Receptor 1 Knockout Deteriorates MK-801-Induced Learning and Memory Impairment in Mice |
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 | Behavioral Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726131/ https://www.ncbi.nlm.nih.gov/pubmed/33324181 http://dx.doi.org/10.3389/fnbeh.2020.00157 |
work_keys_str_mv | AT zhangchun gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT liuqiang gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT yuchunyang gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT wangfeng gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT shaoyu gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT sunkuisheng gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT suntao gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice AT liujuan gproteincoupledestrogenreceptor1knockoutdeterioratesmk801inducedlearningandmemoryimpairmentinmice |