Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus.Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation ...Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus.Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories.Regulation of hippocampal neurogenesis is complex and multifaceted,and numerous signaling pathways converge to modulate cell proliferation,apoptosis,and clearance of cellular debris,as well as synaptic integration of newborn immature neurons.The expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored.P2X7 receptors are exceptionally versatile:in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation.P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication,and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form,which induce apoptotic cell death through cytosolic ion dysregulation.Lastly,as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis,as well as during some disease states.Understanding how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative medicine.This review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus,and neural stem and progenitor cells.展开更多
BACKGROUND Clopidogrel is a widely prescribed drug for prevention of myocardial infarction and stroke in patients at risk.It inhibits thrombus formation via inhibition of the P2Y12 purinergic receptor on platelets,whi...BACKGROUND Clopidogrel is a widely prescribed drug for prevention of myocardial infarction and stroke in patients at risk.It inhibits thrombus formation via inhibition of the P2Y12 purinergic receptor on platelets,which is important in their activation by ADP.However,the P2Y12 receptor has also been found to be expressed in both osteoblasts and osteoclasts.Accumulated evidence suggests that purinergic receptors regulate important functions of bone turnover.Previous studies on the effect of clopidogrel on bone metabolism indicated potential harmful effects,but their results remain conflicting.Thus,clopidogrel treatment may affect bone healing,but it has not yet been studied.AIM To evaluate if continuous perioperative clopidogrel treatment has any negative effect on bone healing in the rabbit calvarial defect model.METHODS Sixteen male white New Zealand rabbits were randomly assigned in two groups:One group received daily 3 mg/kg of clopidogrel per os and the other group received the vehicle alone for a week prior to the surgical procedures;the treatments were continued for another 6 wk postoperatively.The surgical procedures included generation of two circular calvarial defects 11 mm in diameter in every animal.After the 6-wk period of healing,postmortem radiographic and histomorphometric evaluation of the defects was performed.RESULTS Both the surgical procedures and the postoperative period were uneventful and well tolerated by all the animals,without any surgical wound dehiscence,signs of infection or other complication.New bone was formed either inwards from the defect margins or in the central portion of the defect as separated bony islets.While defect healing was still incomplete in both groups,the clopidogrel group had significantly improved radiographic healing scores.Moreover,the histomorphometric analysis showed that bone regeneration(%)was 28.07±7.7 for the clopidogrel group and 19.47±4.9 for the control group,showing a statistically significant difference between them(P=0.018).Statistically significa展开更多
Human immunodeficiency virus(HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T...Human immunodeficiency virus(HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.展开更多
Geoffrey Burnstock completed a BSc at King's College London and a PhD at University College London. He held postdoctoral fellowships with Wilhelm Feldberg(National Institute for Medical Research),Edith Bülbri...Geoffrey Burnstock completed a BSc at King's College London and a PhD at University College London. He held postdoctoral fellowships with Wilhelm Feldberg(National Institute for Medical Research),Edith Bülbring(University of Oxford) and C. Ladd Prosser(University of Illinois) . He was appointed to a Senior Lectureship in Melbourne University in 1959 and became Professor and Chairman of Zoology in 1964. In 1975 he became Head of Department of Anatomy and Developmental Biology at UCL and Convenor of the Center of Neuroscience. He has been Director of the Autonomic Neuroscience Institute at the Royal Free Hospital School of Medicine since 1997. He was elected to the Australian Academy of Sciences in 1971,the Royal Society in 1986,the Academy of Medical Sciences in 1998 and an Honorary Fellow of the Royal College of Surgeons and the Royal College of Physicians in 1999 and 2000. He was awarded the Royal Society Gold Medal in 2000. He is editor-in-chief of the journals Autonomic Neuroscience and Purinergic Signalling and on the editorial boards of many other journals. Geoffrey Burnstock's major research interest has been autonomic neurotransmission and he is best known for his seminal discovery of purinergic transmission and receptors,their signaling pathways and functional relevance. He has supervised over 100 PhD and MD studentsand published over 1400 original papers,re-views and books. He was first in the Institute of Scientific Information list of most cited scientists in Pharmacology and Toxicology from 1994-2004 [59.083 citations(March 2011) and an h-index of 109].展开更多
Purinergic P2X receptors are a family of ligand-gated cationic channels activated by extracellular ATP. P2X subunit protein sequences are highly conserved between vertebrate species. However, they can generate a great...Purinergic P2X receptors are a family of ligand-gated cationic channels activated by extracellular ATP. P2X subunit protein sequences are highly conserved between vertebrate species. However, they can generate a great diversity of coding splicing variants to fulfill several roles in mammalian physiology. Despite intensive research in P2X expression in both central and peripheral nervous system, there is little information about their homology, genomic structure and other key features that can help to develop selective drugs or regulatory strategies of pharmacological value which are lacking today. In order to obtain clues on mammalian P2X diversity, we have performed a bioinformatics analysis of the coding regions and introns of the seven P2X subunits present in human, simian, dog, mouse, rat and zebrafish. Here we report the arrangements of exon and intron sequences, considering its number, size, phase and placement;proposing some ideas about the gain and loss of exons and retention of introns. Taken together, these evidences show traits that can be used to gain insight into the evolutionary history of vertebrate P2X receptors and better understand the diversity of subunits coding the purinergic signaling in mammals.展开更多
文摘Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus.Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories.Regulation of hippocampal neurogenesis is complex and multifaceted,and numerous signaling pathways converge to modulate cell proliferation,apoptosis,and clearance of cellular debris,as well as synaptic integration of newborn immature neurons.The expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored.P2X7 receptors are exceptionally versatile:in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation.P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication,and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form,which induce apoptotic cell death through cytosolic ion dysregulation.Lastly,as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis,as well as during some disease states.Understanding how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative medicine.This review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus,and neural stem and progenitor cells.
文摘BACKGROUND Clopidogrel is a widely prescribed drug for prevention of myocardial infarction and stroke in patients at risk.It inhibits thrombus formation via inhibition of the P2Y12 purinergic receptor on platelets,which is important in their activation by ADP.However,the P2Y12 receptor has also been found to be expressed in both osteoblasts and osteoclasts.Accumulated evidence suggests that purinergic receptors regulate important functions of bone turnover.Previous studies on the effect of clopidogrel on bone metabolism indicated potential harmful effects,but their results remain conflicting.Thus,clopidogrel treatment may affect bone healing,but it has not yet been studied.AIM To evaluate if continuous perioperative clopidogrel treatment has any negative effect on bone healing in the rabbit calvarial defect model.METHODS Sixteen male white New Zealand rabbits were randomly assigned in two groups:One group received daily 3 mg/kg of clopidogrel per os and the other group received the vehicle alone for a week prior to the surgical procedures;the treatments were continued for another 6 wk postoperatively.The surgical procedures included generation of two circular calvarial defects 11 mm in diameter in every animal.After the 6-wk period of healing,postmortem radiographic and histomorphometric evaluation of the defects was performed.RESULTS Both the surgical procedures and the postoperative period were uneventful and well tolerated by all the animals,without any surgical wound dehiscence,signs of infection or other complication.New bone was formed either inwards from the defect margins or in the central portion of the defect as separated bony islets.While defect healing was still incomplete in both groups,the clopidogrel group had significantly improved radiographic healing scores.Moreover,the histomorphometric analysis showed that bone regeneration(%)was 28.07±7.7 for the clopidogrel group and 19.47±4.9 for the control group,showing a statistically significant difference between them(P=0.018).Statistically significa
文摘Human immunodeficiency virus(HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.
文摘Geoffrey Burnstock completed a BSc at King's College London and a PhD at University College London. He held postdoctoral fellowships with Wilhelm Feldberg(National Institute for Medical Research),Edith Bülbring(University of Oxford) and C. Ladd Prosser(University of Illinois) . He was appointed to a Senior Lectureship in Melbourne University in 1959 and became Professor and Chairman of Zoology in 1964. In 1975 he became Head of Department of Anatomy and Developmental Biology at UCL and Convenor of the Center of Neuroscience. He has been Director of the Autonomic Neuroscience Institute at the Royal Free Hospital School of Medicine since 1997. He was elected to the Australian Academy of Sciences in 1971,the Royal Society in 1986,the Academy of Medical Sciences in 1998 and an Honorary Fellow of the Royal College of Surgeons and the Royal College of Physicians in 1999 and 2000. He was awarded the Royal Society Gold Medal in 2000. He is editor-in-chief of the journals Autonomic Neuroscience and Purinergic Signalling and on the editorial boards of many other journals. Geoffrey Burnstock's major research interest has been autonomic neurotransmission and he is best known for his seminal discovery of purinergic transmission and receptors,their signaling pathways and functional relevance. He has supervised over 100 PhD and MD studentsand published over 1400 original papers,re-views and books. He was first in the Institute of Scientific Information list of most cited scientists in Pharmacology and Toxicology from 1994-2004 [59.083 citations(March 2011) and an h-index of 109].
文摘Purinergic P2X receptors are a family of ligand-gated cationic channels activated by extracellular ATP. P2X subunit protein sequences are highly conserved between vertebrate species. However, they can generate a great diversity of coding splicing variants to fulfill several roles in mammalian physiology. Despite intensive research in P2X expression in both central and peripheral nervous system, there is little information about their homology, genomic structure and other key features that can help to develop selective drugs or regulatory strategies of pharmacological value which are lacking today. In order to obtain clues on mammalian P2X diversity, we have performed a bioinformatics analysis of the coding regions and introns of the seven P2X subunits present in human, simian, dog, mouse, rat and zebrafish. Here we report the arrangements of exon and intron sequences, considering its number, size, phase and placement;proposing some ideas about the gain and loss of exons and retention of introns. Taken together, these evidences show traits that can be used to gain insight into the evolutionary history of vertebrate P2X receptors and better understand the diversity of subunits coding the purinergic signaling in mammals.
