Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression
While androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissecti...
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1021 |
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| author | Yi-Yung Hung Ya-Ling Huang Chawnshang Chang Hong-Yo Kang |
| author_facet | Yi-Yung Hung Ya-Ling Huang Chawnshang Chang Hong-Yo Kang |
| author_sort | Yi-Yung Hung |
| collection | DOAJ |
| description | While androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissection indicated that AR might function via altering the expression of miR-204-5p to modulate the brain-derived neurotrophic factor (BDNF) expression to influence the depressive-like behaviors in the mice under the CMS. Adding the antiandrogen flutamide with the stress hormone corticosterone can additively decrease BDNF mRNA in mouse hippocampus mHippoE-14 cells, which can then be reversed via down-regulating the miR-204-5p expression. Importantly, targeting this newly identified AR-mediated miR-204-5p/BDNF/AKT/MAPK signaling with small molecules including 7,8-DHF and fluoxetine, all led to alter the depressive-like behavior in AR knockout mice under CMS exposure. Together, results from these preclinical studies conclude that decreased AR may accelerate the stress-induced MDD via altering miR-204-5p/BDNF/AKT/MAPK signaling, and targeting this newly identified signaling may help in the development of better therapeutic approaches to reduce the development of MDD. |
| first_indexed | 2024-03-12T07:08:05Z |
| format | Article |
| id | doaj.art-60c3e5838b5e4a74a46b20f4f99c7b9c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:08:05Z |
| publishDate | 2019-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-60c3e5838b5e4a74a46b20f4f99c7b9c2023-09-02T23:17:18ZengMDPI AGCells2073-44092019-09-0189102110.3390/cells8091021cells8091021Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of DepressionYi-Yung Hung0Ya-Ling Huang1Chawnshang Chang2Hong-Yo Kang3Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanGeorge Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14646, USAGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, TaiwanWhile androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissection indicated that AR might function via altering the expression of miR-204-5p to modulate the brain-derived neurotrophic factor (BDNF) expression to influence the depressive-like behaviors in the mice under the CMS. Adding the antiandrogen flutamide with the stress hormone corticosterone can additively decrease BDNF mRNA in mouse hippocampus mHippoE-14 cells, which can then be reversed via down-regulating the miR-204-5p expression. Importantly, targeting this newly identified AR-mediated miR-204-5p/BDNF/AKT/MAPK signaling with small molecules including 7,8-DHF and fluoxetine, all led to alter the depressive-like behavior in AR knockout mice under CMS exposure. Together, results from these preclinical studies conclude that decreased AR may accelerate the stress-induced MDD via altering miR-204-5p/BDNF/AKT/MAPK signaling, and targeting this newly identified signaling may help in the development of better therapeutic approaches to reduce the development of MDD.https://www.mdpi.com/2073-4409/8/9/1021major depressive disorderchronic mild stressmiR-204-5pBDNFandrogen receptor |
| spellingShingle | Yi-Yung Hung Ya-Ling Huang Chawnshang Chang Hong-Yo Kang Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression Cells major depressive disorder chronic mild stress miR-204-5p BDNF androgen receptor |
| title | Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression |
| title_full | Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression |
| title_fullStr | Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression |
| title_full_unstemmed | Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression |
| title_short | Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression |
| title_sort | deficiency in androgen receptor aggravates the depressive like behaviors in chronic mild stress model of depression |
| topic | major depressive disorder chronic mild stress miR-204-5p BDNF androgen receptor |
| url | https://www.mdpi.com/2073-4409/8/9/1021 |
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