PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice
Hormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERα and ERβ. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be invol...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-09-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI165812 |
| _version_ | 1827768087245488128 |
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| author | Xinshang Wang Yongli Jiang Ban Feng Xue Ma Kun Zhang Fan Yang Zhenguo Liu Le Yang Jiao Yue Liang Lu Dake Song Qingjuan Guo Jingyu Qi Xubo Li Min Wang Huinan Zhang Jing Huang Minggao Zhao Shuibing Liu |
| author_facet | Xinshang Wang Yongli Jiang Ban Feng Xue Ma Kun Zhang Fan Yang Zhenguo Liu Le Yang Jiao Yue Liang Lu Dake Song Qingjuan Guo Jingyu Qi Xubo Li Min Wang Huinan Zhang Jing Huang Minggao Zhao Shuibing Liu |
| author_sort | Xinshang Wang |
| collection | DOAJ |
| description | Hormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERα and ERβ. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be involved in memory modulation; however, the underlying mechanisms are poorly understood. Here, we found that GPR30 deletion in astrocytes, but not in neurons, impaired learning and memory in female mice. Astrocytic GPR30 depletion induced A1 phenotype transition, impairing neuronal function. Further exploration revealed that Praja1 (PJA1), a RING ubiquitin ligase, mediated the effects of astrocytic GPR30 on learning and memory by binding to Serpina3n, which is a molecular marker of neuroinflammation in astrocytes. GPR30 positively modulated PJA1 expression through the CREB signaling pathway in cultured murine and human astrocytes. Additionally, the mRNA levels of GPR30 and PJA1 were reduced in exosomes isolated from postmenopausal women while Serpina3n levels were increased in the plasma. Together, our findings suggest a key role for astrocytic GPR30 in the learning and memory abilities of female mice and identify GPR30/PJA1/Serpina3n as potential therapeutic targets for learning and memory loss in peri- and postmenopausal women. |
| first_indexed | 2024-03-11T12:07:15Z |
| format | Article |
| id | doaj.art-0de22e0923984db389c2c56cd22dd7a7 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:15Z |
| publishDate | 2023-09-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-0de22e0923984db389c2c56cd22dd7a72023-11-07T16:20:51ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-09-0113318PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female miceXinshang WangYongli JiangBan FengXue MaKun ZhangFan YangZhenguo LiuLe YangJiao YueLiang LuDake SongQingjuan GuoJingyu QiXubo LiMin WangHuinan ZhangJing HuangMinggao ZhaoShuibing LiuHormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERα and ERβ. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be involved in memory modulation; however, the underlying mechanisms are poorly understood. Here, we found that GPR30 deletion in astrocytes, but not in neurons, impaired learning and memory in female mice. Astrocytic GPR30 depletion induced A1 phenotype transition, impairing neuronal function. Further exploration revealed that Praja1 (PJA1), a RING ubiquitin ligase, mediated the effects of astrocytic GPR30 on learning and memory by binding to Serpina3n, which is a molecular marker of neuroinflammation in astrocytes. GPR30 positively modulated PJA1 expression through the CREB signaling pathway in cultured murine and human astrocytes. Additionally, the mRNA levels of GPR30 and PJA1 were reduced in exosomes isolated from postmenopausal women while Serpina3n levels were increased in the plasma. Together, our findings suggest a key role for astrocytic GPR30 in the learning and memory abilities of female mice and identify GPR30/PJA1/Serpina3n as potential therapeutic targets for learning and memory loss in peri- and postmenopausal women.https://doi.org/10.1172/JCI165812InflammationNeuroscience |
| spellingShingle | Xinshang Wang Yongli Jiang Ban Feng Xue Ma Kun Zhang Fan Yang Zhenguo Liu Le Yang Jiao Yue Liang Lu Dake Song Qingjuan Guo Jingyu Qi Xubo Li Min Wang Huinan Zhang Jing Huang Minggao Zhao Shuibing Liu PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice The Journal of Clinical Investigation Inflammation Neuroscience |
| title | PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice |
| title_full | PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice |
| title_fullStr | PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice |
| title_full_unstemmed | PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice |
| title_short | PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice |
| title_sort | pja1 mediates the effects of astrocytic gpr30 on learning and memory in female mice |
| topic | Inflammation Neuroscience |
| url | https://doi.org/10.1172/JCI165812 |
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