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| 1 | Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT2B Receptors and Triggers Depressive-Like Behaviors via Stimulating P2X7 Receptors in Mice显示文摘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 P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-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 P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders. | Maosheng Xia Zexiong Li Shuai Li Shanshan Liang Xiaowei Li Beina Chen Manman Zhang Chengyi Dong Alexei Verkhratsky Dawei Guan Baoman Li | 2020 | Neuroscience Bulletin2020,36,11: | 10 |
| 2 | Iron Aggravates the Depressive Phenotype of Stressed Mice by Compromising the Glymphatic System显示文摘Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1]. | Shanshan Liang Yan Lu Zexiong Li Shuai Li Beina Chen Manman Zhang Binjie Chen Ming Ji Wenliang Gong Maosheng Xia Alexei Verkhratsky Xu Wu Baoman Li | 2020 | Neuroscience Bulletin2020,36,12: | 5 |
| 3 | Astrocytes in Post-traumatic Stress Disorder显示文摘Although posttraumatic stress disorder(PTSD)is on the rise,traumatic events and their consequences are often hidden or minimized by patients for reasons linked to PTSD itself.Traumatic experiences can be broadly classified into mental stress(MS)and traumatic brain injury(TBI),but the cellular mechanisms of MS-or TBI-induced PTSD remain unknown.Recent evidence has shown that the morphological remodeling of astrocytes accompanies and arguably contributes to fearful memories and stressrelated disorders.In this review,we summarize the roles of astrocytes in the pathogenesis of MS-PTSD and TBIPTSD.Astrocytes synthesize and secrete neurotrophic,proand anti-inflammatory factors and regulate the microenvironment of the nervous tissue through metabolic pathways,ionostatic control,and homeostatic clearance of neurotransmitters.Stress or trauma-associated impairment of these vital astrocytic functions contribute to the pathophysiological evolution of PTSD and may present therapeutic targets. | Baoman Li Dianjun Zhang Alexei Verkhratsky | 2022 | Neuroscience Bulletin2022,38,8: | 1 |
| 4 | Astrocytes in human central nervous system diseases: a frontier for new therapies显示文摘Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome.Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions.Astroglia respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and function.In addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS pathologies.Astroglial pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and sex.Here,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive disease.We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric disorders.Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies. | Alexei Verkhratsky Arthur Butt Baoman Li Peter Illes Robert Zorec Alexey Semyanov Yong Tang Michael V.Sofroniew | 2023 | Signal Transduction and Targeted Therapy2023,8,11: | 0 |