Purinergic receptors are among the first cell surface receptors expressed during embryonic development （Burnstock and Ulrich, 2011）. These are characterized based on their pharmacological properties of being activat...Purinergic receptors are among the first cell surface receptors expressed during embryonic development （Burnstock and Ulrich, 2011）. These are characterized based on their pharmacological properties of being activated by adenosine or purine/pyrimidine nucleotides as P1 and P2 receptors. P2 receptors are further classified by their structure as P2Y metabotropic and P2X ionotropic receptors.展开更多
Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belong...Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）.展开更多
Social hierarchy is a general self-organizational scheme in animal societies in which each member achieves a certain status of domination or subordination when getting access to resources,with profound consequences fo...Social hierarchy is a general self-organizational scheme in animal societies in which each member achieves a certain status of domination or subordination when getting access to resources,with profound consequences for survival,health,reproductive success,and multiple behaviors[1,2].The prefrontal cortex(PFC)was recognized as a central regulator of neuronal circuits determining the formation of social hierarchy;brain areas upstream of the PFC convey information about social status,and downstream brain regions execute dominance behavior[3].Social deficits have been suggested to be due to an elevation of excitatory/inhibitory(E/l)balance within the mouse dorsomedial(dm)PFC[4].A compensatory increase of inhibitory cell excitability partially rescued social deficits caused by such a disturbance of E/l balance.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
Purines and their derivatives,most notably adenosine and ATP,are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis.Besides,these purines support,as chemical messengers,purinergic...Purines and their derivatives,most notably adenosine and ATP,are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis.Besides,these purines support,as chemical messengers,purinergic transmission throughout tissues and species.Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors,which mediate extracellular communication referred to as“purinergic signalling”.Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation,differentiation,migration,apoptosis and other physiological processes critical for the proper function of organisms.Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration,rheumatic immune diseases,inflammation,and cancer.Particularly,gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia.Compelling evidence indicates that purinoceptors are potential therapeutic targets,with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential.Furthermore,dietary and herbal interventions help to restore and balance purine metabolism,thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders.Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.展开更多
Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,respectivel...Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,respectively.We review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative diseases.The adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor inhibition.Furthermore,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor subtype.This interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal damage.Thus,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD.展开更多
Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it repre...Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it represents not only a personal hardship for the patients themselves,but also a major socio-economic burden for society as a whole.展开更多
The existence of purinergic signaling—the idea that almost all cells of the animal/human organism are able to communicate with each other via extracellular purines—was proposed by Geoffrey Burnstock(1929-2020)in 197...The existence of purinergic signaling—the idea that almost all cells of the animal/human organism are able to communicate with each other via extracellular purines—was proposed by Geoffrey Burnstock(1929-2020)in 1972[1-3].The purinergic system includes the following constituents:(1)the four main purines:adenosine triphosphate(ATP)and its metabolites,adenosine diphosphate(ADP),adenosine monophosphate(AMP),and adenosine(ADO);(2)three key enzymes,the ectonucleoside triphosphate diphosphohydrolases(E-NTPDases:NTPDase1/CD39),ectonucleotide pyrophosphatase/phosphodiesterases(E-NPP),and ecto-5’-nucleotidase(E-5’-nucleotidase/CD73),which decompose ATP into ADP,AMP,and ADO.展开更多
In the central nervous system,purinergic signaling plays an important role in maintaining the functions of neurons,astrocytes,and microglia,thereby regulating brain homeostasis,with consequences for higher-order cogni...In the central nervous system,purinergic signaling plays an important role in maintaining the functions of neurons,astrocytes,and microglia,thereby regulating brain homeostasis,with consequences for higher-order cognitive processes[1].ATP released from astrocytes in conjunction with several additional signaling molecules modulates neuronal circuits.展开更多
Morphine and other opioids are among the most effective analgesics for treating pain.However,drug dependence and other deleterious side effects of opioids have limited their clinical applicability.Recent studies sugge...Morphine and other opioids are among the most effective analgesics for treating pain.However,drug dependence and other deleterious side effects of opioids have limited their clinical applicability.Recent studies suggest that the use of opioids for pain control may even exacerbate disease outcomes in some pain-producing conditions,such as acute pancreatitis[1].展开更多
Recently,a paper published in Science reported discovery of sensory peripheral glial cells[1].This paper demonstrated a rather unexpected property of non-myelinating Schwann cells(also known as Remak cells)dwelling in...Recently,a paper published in Science reported discovery of sensory peripheral glial cells[1].This paper demonstrated a rather unexpected property of non-myelinating Schwann cells(also known as Remak cells)dwelling in the subepidermal border of the skin[2].These glial cells and their interactions with nociceptive nerve terminals were characterized using a variety of genetic labelling tools,transmission electron microscopy,immunocytochemistry.展开更多
The recent paper published in Nature by Badimon et al.demonstrates that neuronal activity via the stimulation of surveilling microglia feeds back to inhibit neuronal networks.1 This effect is mediated by the release o...The recent paper published in Nature by Badimon et al.demonstrates that neuronal activity via the stimulation of surveilling microglia feeds back to inhibit neuronal networks.1 This effect is mediated by the release of ATP from the terminals of excitatory neurons;subsequently,ATP is degraded to adenosine by microglial enzymes,imposing an inhibitory,A1 receptor(R)-mediated control on the hyperactive neurons themselves.展开更多
The paper,published recently in Nature by the group of Francisco Quintana,1 describes the anti-inflammatory astrocytes,activity of which is tuned by the microbiotome and meningeal natural killer(NK)cells.Astrocytes ar...The paper,published recently in Nature by the group of Francisco Quintana,1 describes the anti-inflammatory astrocytes,activity of which is tuned by the microbiotome and meningeal natural killer(NK)cells.Astrocytes are a sub-type of neuroglia responsible for homoeostasis and defence of the nervous system.Pathological reactions of neuroglial cells in various neurological disorders have been identified and characterised in the end of the 19th century;in particular hypertrophy of astrocytes was recognised as a frequent morbid change accompanying diseases of the central nervous system(CNS).展开更多
基金support from Fundacao de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)+2 种基金the Provost’s Office for Research of the University of Sao Paulo, Grant number: 2011.1.9333.1.3 (NAPNA-USP)support from the German Research Council (IL 20/182, RI 2092/1-2, IL 20/21-1)the Sino-German Centre for the Support of Science (GZ 919)
文摘Purinergic receptors are among the first cell surface receptors expressed during embryonic development （Burnstock and Ulrich, 2011）. These are characterized based on their pharmacological properties of being activated by adenosine or purine/pyrimidine nucleotides as P1 and P2 receptors. P2 receptors are further classified by their structure as P2Y metabotropic and P2X ionotropic receptors.
基金supported by Deutsche Forschungsgemeinschaft(DFGIL 20/21-1)Sino-German Centre(GZ919)
文摘Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）.
基金supported by a grant from the Chengdu University of TCM(CZYHW1901)to build up the International Joint Research Center on Purinergic Signaling。
文摘Social hierarchy is a general self-organizational scheme in animal societies in which each member achieves a certain status of domination or subordination when getting access to resources,with profound consequences for survival,health,reproductive success,and multiple behaviors[1,2].The prefrontal cortex(PFC)was recognized as a central regulator of neuronal circuits determining the formation of social hierarchy;brain areas upstream of the PFC convey information about social status,and downstream brain regions execute dominance behavior[3].Social deficits have been suggested to be due to an elevation of excitatory/inhibitory(E/l)balance within the mouse dorsomedial(dm)PFC[4].A compensatory increase of inhibitory cell excitability partially rescued social deficits caused by such a disturbance of E/l balance.
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This article is dedicated to the memory of recently deceased Professor Geoffrey Burnstock.This work was supported by grants from National Key R&D Programme of China(2019YFC1709101,2020YFA0509400,2020YFC2002705)the National Natural Science Foundation of China(81821002,81790251,81373735,81972665)+5 种基金Guangdong Basic and Applied Basic Research Foundation(2019B030302012)the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine(CZYHW1901)Sao Paulo Research Foundation(FAPESP 2018/07366-4)NSFC and RFBR(project number 21-54-53018,82111530059)MDT programme of State Administration of Traditional Chinese MedicineScience and Technology Programme of Sichuan Province,China(2019YFH0108,2021JDGD0037).
文摘Purines and their derivatives,most notably adenosine and ATP,are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis.Besides,these purines support,as chemical messengers,purinergic transmission throughout tissues and species.Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors,which mediate extracellular communication referred to as“purinergic signalling”.Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation,differentiation,migration,apoptosis and other physiological processes critical for the proper function of organisms.Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration,rheumatic immune diseases,inflammation,and cancer.Particularly,gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia.Compelling evidence indicates that purinoceptors are potential therapeutic targets,with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential.Furthermore,dietary and herbal interventions help to restore and balance purine metabolism,thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders.Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.
基金the Sao Paulo Research Foundation(FAPESP,2018/07366-4)a Fellowship from the National Council for Scientific and Technological Development(CNPq,306392/2017-8)+5 种基金postdoctoral fellowships from FAPESP(2015/13345-1,2019/268520,and 2018/17504-5)a doctoral fellowship from FAPESP(2019/24553-5)a master fellowship from CNPq(133396/2019-3)the fellowship from National Key R&D Program of China(2019YFC1709101)The Project First-Class Disciplines Development(CZYHW1901)of Chengdu University of TCM and Sichuan Science and Technology Program(2019YFH0108,2018SZ0257)supported by Russian Science Foundation grant 20-14-00241。
文摘Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,respectively.We review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative diseases.The adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor inhibition.Furthermore,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor subtype.This interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal damage.Thus,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD.
基金The Project First-Class Disciplines Development of Chengdu University of TCM(CZYHW1901)the National Natural Science Foundation of China(81774437,81973969)the Science and Technology Program of Sichuan Province,China(2019YFH0108,2018SZ0257)。
文摘Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it represents not only a personal hardship for the patients themselves,but also a major socio-economic burden for society as a whole.
基金the National Key R&D Program of China(2019YFC1709101)the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine(CZYHW1901)the Science and Technology Program of Sichuan Province,China(2019YFH0108)。
文摘The existence of purinergic signaling—the idea that almost all cells of the animal/human organism are able to communicate with each other via extracellular purines—was proposed by Geoffrey Burnstock(1929-2020)in 1972[1-3].The purinergic system includes the following constituents:(1)the four main purines:adenosine triphosphate(ATP)and its metabolites,adenosine diphosphate(ADP),adenosine monophosphate(AMP),and adenosine(ADO);(2)three key enzymes,the ectonucleoside triphosphate diphosphohydrolases(E-NTPDases:NTPDase1/CD39),ectonucleotide pyrophosphatase/phosphodiesterases(E-NPP),and ecto-5’-nucleotidase(E-5’-nucleotidase/CD73),which decompose ATP into ADP,AMP,and ADO.
基金This Research Highlight was supported by a generous grant(“The project First-Class Disciplines Development”CZYHW1901)of the Chengdu University of Traditional Chinese Medicine in order to build up the“International Collaborative Centre on Big Science Plan for Purinergic Signalling”and grants of the State Administration of Foreign Experts Affairs to support the stay of PR and PI in Chengdu(G20190236012)+1 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202003)Sichuan Science and Technology Program(2019YFH0108).
文摘In the central nervous system,purinergic signaling plays an important role in maintaining the functions of neurons,astrocytes,and microglia,thereby regulating brain homeostasis,with consequences for higher-order cognitive processes[1].ATP released from astrocytes in conjunction with several additional signaling molecules modulates neuronal circuits.
基金supported by the National Key R&D Program of China (2019YFC1709101)The Project First-Class Disciplines Development of Chengdu University of TCM (CZYHW1901)+2 种基金Sao Paulo Research Foundation (FAPESP 2018/07366-4)the National Natural Science Foundation of China (81904312 and 81774437)the Sichuan Science and Technology Program,China (2019YFH0108,2018HH0123,and 2018SZ0257)。
文摘Morphine and other opioids are among the most effective analgesics for treating pain.However,drug dependence and other deleterious side effects of opioids have limited their clinical applicability.Recent studies suggest that the use of opioids for pain control may even exacerbate disease outcomes in some pain-producing conditions,such as acute pancreatitis[1].
基金supported by National Key R&D Program of China(2019YFC1709101)the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine(CZYHW1901)+1 种基金the National Natural Science Foundation of China(81774437 and 81973969)Science and Technology Program of Sichuan Province,China(2019YFH0108 and 2018SZ0257)。
文摘Recently,a paper published in Science reported discovery of sensory peripheral glial cells[1].This paper demonstrated a rather unexpected property of non-myelinating Schwann cells(also known as Remak cells)dwelling in the subepidermal border of the skin[2].These glial cells and their interactions with nociceptive nerve terminals were characterized using a variety of genetic labelling tools,transmission electron microscopy,immunocytochemistry.
基金This work was supported by grants of the National Key R&D Program of China(2019YFC1709101)the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine(CZYHW1901)+1 种基金awarded in order to build up the“International Collaborative Centre on Big Science Plan for Purine Signalling”,and the Science and Technology Program of Sichuan Province,China(2019YFH0108)The stay and work of P.I.in Chengdu was supported by a grant of the State Administration of Foreign Experts Affairs(G20190236012).
文摘The recent paper published in Nature by Badimon et al.demonstrates that neuronal activity via the stimulation of surveilling microglia feeds back to inhibit neuronal networks.1 This effect is mediated by the release of ATP from the terminals of excitatory neurons;subsequently,ATP is degraded to adenosine by microglial enzymes,imposing an inhibitory,A1 receptor(R)-mediated control on the hyperactive neurons themselves.
基金This work was supported by grants of the National Key R&D Programme of China(2019YFC1709101)the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine(CZYHW1901)awarded in order to build up the“International Collaborative Centre on Big Science Plan for Purinergic Signalling”,and the Science and Technology Programme of Sichuan Province,China(2019YFH0108)+1 种基金The stay and work of PI in Chengdu was supported by a grant from the State Administration of Foreign Experts Affairs(G20190236012)A.S.and Y.T.are supported by RFBR grant 21-54-53018 for the NSFC-RFBR project.
文摘The paper,published recently in Nature by the group of Francisco Quintana,1 describes the anti-inflammatory astrocytes,activity of which is tuned by the microbiotome and meningeal natural killer(NK)cells.Astrocytes are a sub-type of neuroglia responsible for homoeostasis and defence of the nervous system.Pathological reactions of neuroglial cells in various neurological disorders have been identified and characterised in the end of the 19th century;in particular hypertrophy of astrocytes was recognised as a frequent morbid change accompanying diseases of the central nervous system(CNS).
