Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT(2B) Receptors and Triggers Depressive-Like Behaviors via Stimulating P2X(7) Receptors in Mice
| Autor: | Dawei Guan, Chengyi Dong, Xiaowei Li, Shanshan Liang, Beina Chen, Alexei Verkhratsky, Manman Zhang, Baoman Li, Shuai Li, Maosheng Xia, Zexiong Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor medicine.medical_specialty Serotonin Physiology Stimulation 03 medical and health sciences Mice 0302 clinical medicine Phospholipase A2 Adenosine Triphosphate Internal medicine Receptor Serotonin 5-HT2B medicine Animals Prostaglandin E2 Receptor biology business.industry Depression General Neuroscience Forkhead Box Protein O3 General Medicine Mice Inbred C57BL Oncogene Protein v-akt Sleep deprivation 030104 developmental biology medicine.anatomical_structure Endocrinology Astrocytes biology.protein Quality of Life Phosphorylation Sleep Deprivation Original Article Receptors Purinergic P2X7 medicine.symptom business 030217 neurology & neurosurgery Astrocyte medicine.drug |
| Zdroj: | Neurosci Bull |
| Popis: | Chronic loss of sleep damages health and disturbs the quality of life. Long-lasting sleep deprivation (SD) as well as sleep abnormalities are substantial risk factors for major depressive disorder, although the underlying mechanisms are not clear. Here, we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP, which activates astroglial P2X(7) receptors (P2X(7)Rs). Activated P2X(7)Rs, in turn, selectively down-regulated the expression of 5-HT(2B) receptors (5-HT(2B)Rs) in astrocytes. Stimulation of P2X(7)Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3a in astrocytes, but not in neurons. The over-expression of FoxO3a in astrocytes inhibited the expression of 5-HT(2B)Rs. Down-regulation of 5-HT(2Bs)Rs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca(2+)-dependent phospholipase A2. This latter cascade promoted the release of arachidonic acid and prostaglandin E2. The depression-like behaviors induced by SD were alleviated in P2X(7)R-KO mice. Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT(2B)Rs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders. |
| Databáze: | OpenAIRE |
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