NDLI: Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors

Content Provider	Springer Nature : BioMed Central
Author	Wang, Bin Shi, Haixia Ren, Liyan Miao, Zhigang Wan, Bo Yang, Hao Fan, Xiaotang Gustafsson, Jan-Ake Sun, Miao Xu, Xingshun
Abstract	Background Depression is one of the most common psychiatric diseases. The monoamine transmitter theory suggests that neurotransmitters are involved in the mechanism of depression; however, the regulation on serotonin production is still unclear. We previously showed that Ahi1 knockout (KO) mice exhibited depression-like behavior accompanied by a significant decrease in brain serotonin. Methods In the present study, western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, and rescue assay were used to detect changes in the Ahi1/GR/ERβ/TPH2 pathway in the brains of male stressed mice and male Ahi1 KO mice to explain the pathogenesis of depression-like behaviors. In addition, E2 levels in the blood and brain of male and female mice were measured to investigate the effect on the ERβ/TPH2 pathway and to reveal the mechanisms for the phenomenon of gender differences in depression-like behaviors. Results We found that the serotonin-producing pathway-the ERβ/TPH2 pathway was inhibited in male stressed mice and male Ahi1 KO mice. We further demonstrated that glucocorticoid receptor (GR) as a transcription factor bound to the promoter of ERβ that contains glucocorticoid response elements and inhibited the transcription of ERβ. Our recent study had indicated that Ahi1 regulates the nuclear translocation of GR upon stress, thus proposing the Ahi1/GR/ERβ/TPH2 pathway for serotonin production. Interestingly, female Ahi1 KO mice did not exhibit depressive behaviors, indicating sexual differences in depressive behaviors compared with male mice. Furthermore, we found that serum 17β-estradiol (E2) level was not changed in male and female mice; however, brain E2 level significantly decreased in male but not female Ahi1 KO mice. Further, ERβ agonist LY-500307 increased TPH2 expression and 5-HT production. Therefore, both Ahi1 and E2 regulate the ERβ/TPH2 pathway and involve sexual differences in brain serotonin production and depressive behaviors. Conclusions In conclusion, although it is unclear how Ahi1 controls E2 secretion in the brain, our findings demonstrate that Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway in the brain and possibly involves the regulation on sex differences in depressive behaviors. Video Abstract
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-022-00894-4.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12964-022-00894-4
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2022-05-28
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Ahi1 Serotonin TPH2 ERβ GR Estrogen
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The mitochondrial Ahi1/GR participates the regulation on mtDNA copy numbers and brain ATP levels and modulates depressive behaviors in mice

Wnt signaling regulates chemokine production and cell migration of circulating human monocytes

CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway

PKCδ regulates the vascular biology in diabetic atherosclerosis

Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway

MST4 negatively regulates type I interferons production via targeting MAVS-mediated pathway

Notch pathway: a bistable inducer of biological noise?

Beyond journal impact factors?

Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors

Similar Documents

The mitochondrial Ahi1/GR participates the regulation on mtDNA copy numbers and brain ATP levels and modulates depressive behaviors in mice

Wnt signaling regulates chemokine production and cell migration of circulating human monocytes

CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway

PKCδ regulates the vascular biology in diabetic atherosclerosis

Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway

MST4 negatively regulates type I interferons production via targeting MAVS-mediated pathway

Notch pathway: a bistable inducer of biological noise?

Beyond journal impact factors?

Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors