Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development
Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone l...
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| Format: | Article |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1140796/full |
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| author | Qian Gao Qian Gao Qian Gao Wei Sun Wei Sun Yue-Rui Wang Yue-Rui Wang Yue-Rui Wang Zi-Fa Li Zi-Fa Li Feng Zhao Feng Zhao Xi-Wen Geng Xi-Wen Geng Xi-Wen Geng Kai-Yong Xu Dan Chen Kun Liu Kun Liu Kun Liu Ying Xing Ying Xing Ying Xing Wei Liu Sheng Wei Sheng Wei Sheng Wei |
| author_facet | Qian Gao Qian Gao Qian Gao Wei Sun Wei Sun Yue-Rui Wang Yue-Rui Wang Yue-Rui Wang Zi-Fa Li Zi-Fa Li Feng Zhao Feng Zhao Xi-Wen Geng Xi-Wen Geng Xi-Wen Geng Kai-Yong Xu Dan Chen Kun Liu Kun Liu Kun Liu Ying Xing Ying Xing Ying Xing Wei Liu Sheng Wei Sheng Wei Sheng Wei |
| author_sort | Qian Gao |
| collection | DOAJ |
| description | Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD. |
| first_indexed | 2024-04-10T06:21:31Z |
| format | Article |
| id | doaj.art-4d526f2b257f40fb9b7412729bc64414 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-10T06:21:31Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-4d526f2b257f40fb9b7412729bc644142023-03-02T04:56:23ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-03-011410.3389/fpsyt.2023.11407961140796Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug developmentQian Gao0Qian Gao1Qian Gao2Wei Sun3Wei Sun4Yue-Rui Wang5Yue-Rui Wang6Yue-Rui Wang7Zi-Fa Li8Zi-Fa Li9Feng Zhao10Feng Zhao11Xi-Wen Geng12Xi-Wen Geng13Xi-Wen Geng14Kai-Yong Xu15Dan Chen16Kun Liu17Kun Liu18Kun Liu19Ying Xing20Ying Xing21Ying Xing22Wei Liu23Sheng Wei24Sheng Wei25Sheng Wei26Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Encephalopathy, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, ChinaChinese Medicine and Brain Science Core Facility, Shandong University of Traditional Chinese Medicine, Jinan, ChinaPremenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1140796/fullpremenstrual dysphoric disorderpremenstrual syndromepathogenesisallopregnanoloneγ-aminobutyric acid A receptorsubunit |
| spellingShingle | Qian Gao Qian Gao Qian Gao Wei Sun Wei Sun Yue-Rui Wang Yue-Rui Wang Yue-Rui Wang Zi-Fa Li Zi-Fa Li Feng Zhao Feng Zhao Xi-Wen Geng Xi-Wen Geng Xi-Wen Geng Kai-Yong Xu Dan Chen Kun Liu Kun Liu Kun Liu Ying Xing Ying Xing Ying Xing Wei Liu Sheng Wei Sheng Wei Sheng Wei Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development Frontiers in Psychiatry premenstrual dysphoric disorder premenstrual syndrome pathogenesis allopregnanolone γ-aminobutyric acid A receptor subunit |
| title | Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development |
| title_full | Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development |
| title_fullStr | Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development |
| title_full_unstemmed | Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development |
| title_short | Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development |
| title_sort | role of allopregnanolone mediated γ aminobutyric acid a receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder toward precise targets for translational medicine and drug development |
| topic | premenstrual dysphoric disorder premenstrual syndrome pathogenesis allopregnanolone γ-aminobutyric acid A receptor subunit |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1140796/full |
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