Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation
The long-lasting loss of sleep is a generally acknowledged risk factor for the occurrence of major depressive disorder (MDD), whereas sleep abnormalities being a key clinic symptom of the MDD. In our previous work, we demonstrated that the sleep deprivation (SD) stimulates activation of nucleotide-b...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-01-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00734/full |
| _version_ | 1818910931771457536 |
|---|---|
| author | Xiaowei Li Shanshan Liang Zexiong Li Shuai Li Maosheng Xia Alexei Verkhratsky Alexei Verkhratsky Baoman Li |
| author_facet | Xiaowei Li Shanshan Liang Zexiong Li Shuai Li Maosheng Xia Alexei Verkhratsky Alexei Verkhratsky Baoman Li |
| author_sort | Xiaowei Li |
| collection | DOAJ |
| description | The long-lasting loss of sleep is a generally acknowledged risk factor for the occurrence of major depressive disorder (MDD), whereas sleep abnormalities being a key clinic symptom of the MDD. In our previous work, we demonstrated that the sleep deprivation (SD) stimulates activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomes as well as the release of IL-1β and IL-18 from astrocytes. However, the underlying mechanism connecting SD and MDD still requires further study. Apart of the secretion of the pro-inflammatory cytokines, SD affects production of brain-derived neurotrophic factor (BDNF) while release of BDNF from astrocytes appears a key contributor to mood disorders. If and how the activation of NLRP3 inflammasome following SD affects the level of BDNF remains unknown. Antidepressant fluoxetine acts through astroglial 5-hydroxytryptamine receptor 2B (5-HT2B); these receptors are also related to the sleep-wake cycle. Contribution of leptin to MDD has been discovered recently, although the mechanistic links between leptin and the depressive-like behaviors has not been revealed. In this study, we discovered: (i) that activation of NLRP3 inflammasome was involved in the depressive-like behaviors induced by SD; (ii) decrease in BDNF following SD required the activation of NLRP3 inflammasomes; (iii) leptin augmented the anti-depressive action of fluoxetine through an increase in expression of astrocytic 5-HT2B receptors. We suggest that decrease in BDNF by the activated NLRP3 inflammasomes in astrocytes is the key pathological event of the depressive-like behaviors induced by SD, while the combined treatment with fluoxetine and leptin improves therapeutic outcome for the depression induced by SD. |
| first_indexed | 2024-12-19T22:50:39Z |
| format | Article |
| id | doaj.art-ca78e833b827452099cc2092105ba729 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-19T22:50:39Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-ca78e833b827452099cc2092105ba7292022-12-21T20:02:49ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402019-01-01910.3389/fpsyt.2018.00734430121Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep DeprivationXiaowei Li0Shanshan Liang1Zexiong Li2Shuai Li3Maosheng Xia4Alexei Verkhratsky5Alexei Verkhratsky6Baoman Li7Laboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, ChinaLaboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, ChinaLaboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, ChinaLaboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, ChinaDepartment of Orthopaedics, The First Hospital, China Medical University, Shenyang, ChinaFaculty of Life Science, The University of Manchester, Manchester, United KingdomAchucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, Bilbao, SpainLaboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, ChinaThe long-lasting loss of sleep is a generally acknowledged risk factor for the occurrence of major depressive disorder (MDD), whereas sleep abnormalities being a key clinic symptom of the MDD. In our previous work, we demonstrated that the sleep deprivation (SD) stimulates activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomes as well as the release of IL-1β and IL-18 from astrocytes. However, the underlying mechanism connecting SD and MDD still requires further study. Apart of the secretion of the pro-inflammatory cytokines, SD affects production of brain-derived neurotrophic factor (BDNF) while release of BDNF from astrocytes appears a key contributor to mood disorders. If and how the activation of NLRP3 inflammasome following SD affects the level of BDNF remains unknown. Antidepressant fluoxetine acts through astroglial 5-hydroxytryptamine receptor 2B (5-HT2B); these receptors are also related to the sleep-wake cycle. Contribution of leptin to MDD has been discovered recently, although the mechanistic links between leptin and the depressive-like behaviors has not been revealed. In this study, we discovered: (i) that activation of NLRP3 inflammasome was involved in the depressive-like behaviors induced by SD; (ii) decrease in BDNF following SD required the activation of NLRP3 inflammasomes; (iii) leptin augmented the anti-depressive action of fluoxetine through an increase in expression of astrocytic 5-HT2B receptors. We suggest that decrease in BDNF by the activated NLRP3 inflammasomes in astrocytes is the key pathological event of the depressive-like behaviors induced by SD, while the combined treatment with fluoxetine and leptin improves therapeutic outcome for the depression induced by SD.https://www.frontiersin.org/article/10.3389/fpsyt.2018.00734/fullsleep deprivation5-HT2B receptorsastrocytesfluoxetineleptinNLRP3 inflammasomes |
| spellingShingle | Xiaowei Li Shanshan Liang Zexiong Li Shuai Li Maosheng Xia Alexei Verkhratsky Alexei Verkhratsky Baoman Li Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation Frontiers in Psychiatry sleep deprivation 5-HT2B receptors astrocytes fluoxetine leptin NLRP3 inflammasomes |
| title | Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation |
| title_full | Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation |
| title_fullStr | Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation |
| title_full_unstemmed | Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation |
| title_short | Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation |
| title_sort | leptin increases expression of 5 ht2b receptors in astrocytes thus enhancing action of fluoxetine on the depressive behavior induced by sleep deprivation |
| topic | sleep deprivation 5-HT2B receptors astrocytes fluoxetine leptin NLRP3 inflammasomes |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00734/full |
| work_keys_str_mv | AT xiaoweili leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT shanshanliang leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT zexiongli leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT shuaili leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT maoshengxia leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT alexeiverkhratsky leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT alexeiverkhratsky leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation AT baomanli leptinincreasesexpressionof5ht2breceptorsinastrocytesthusenhancingactionoffluoxetineonthedepressivebehaviorinducedbysleepdeprivation |