Worldwide,the incidence of major depressive disorder(MDD)is increasing annually,resulting in greater economic and social burdens.Moreover,the pathological mechanisms of MDD and the mechanisms underlying the effects of...Worldwide,the incidence of major depressive disorder(MDD)is increasing annually,resulting in greater economic and social burdens.Moreover,the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear,and additional diagnostic and therapeutic strategies for MDD still are needed.The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis,hypothalamicpituitary-adrenal(HPA)axis hypothesis,cytokine hypothesis,neuroplasticity hypothesis and systemic influence hypothesis,but these hypothesis cannot completely explain the pathological mechanism of MDD.Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD,thus in recent years,great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies,further revealing the disease features of MDD.Furthermore,some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention,some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms.In this work,we comprehensively summarize the latest research on the pathogenesis and diagnosis of MDD,preventive approaches and therapeutic medicines,as well as the related clinical trials.展开更多
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...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.展开更多
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 neuropsych...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.展开更多
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 syste...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].展开更多
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 class...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.展开更多
基金supported by the National Natural Science Foundation of China,MX[grant number 32271038]and BL[grant number 81871852]Shenyang Science and Technology Innovation Talents Project,BL[grant number RC210251]+2 种基金‘ChunHui’Program of Education Ministry,BL[grant number 2020703]National Natural Science Foundation of China-Russian Science Foundation(NSFC-RSF),YT[grant number 82261138557]Sichuan Provincial Administration of Traditional Chinese Medicine,YT[grant number 2023zd024].
文摘Worldwide,the incidence of major depressive disorder(MDD)is increasing annually,resulting in greater economic and social burdens.Moreover,the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear,and additional diagnostic and therapeutic strategies for MDD still are needed.The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis,hypothalamicpituitary-adrenal(HPA)axis hypothesis,cytokine hypothesis,neuroplasticity hypothesis and systemic influence hypothesis,but these hypothesis cannot completely explain the pathological mechanism of MDD.Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD,thus in recent years,great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies,further revealing the disease features of MDD.Furthermore,some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention,some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms.In this work,we comprehensively summarize the latest research on the pathogenesis and diagnosis of MDD,preventive approaches and therapeutic medicines,as well as the related clinical trials.
基金the National Natural Science Foundation of China(81871852,81200935,81671862,and 81871529)Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Overseas Scholars of the Education Ministry of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
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.
基金grants from NSFC-RSF(82261138557)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202003)+3 种基金the Sichuan Science and Technology Program(2022YFH0006)Y.T.was supported by NSFC(82274668,82230127)Sichuan Provincial Administration of Traditional Chinese Medicine(2023zd024).Work in the M.V.S.laboratory is supported by National Institutes of Health(NS084030)by the Dr.Miriam and Sheldon G.Adelson Medical Foundation.
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.
基金the National Natural Science Foundation of China(81871852,81200935,81671867 and 81971794)the Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Returned Scholars of the Ministry of Education of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
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].
基金This review was supported by the National Natural Science Foundation of China,(81871852)Shenyang Science and Technology Innovation Talents Project(RC210251)+3 种基金Liaoning Revitalization Talents Program(XLYC1807137)the Scientific Research Foundation for Returned Scholars of Education Ministry of China(20151098)Liaoning Thousand Talents Program(202078)the"Chunhui"Program of Education Ministry(2020703).
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.