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
Dysfunctional autophagy often occurs during the development of neurodegenerative diseases,such as Parkinson’s disease,Huntington’s disease,and Alzheimer’s disease.The purinergic P2X4 receptor is an ATP-gated ion ch...Dysfunctional autophagy often occurs during the development of neurodegenerative diseases,such as Parkinson’s disease,Huntington’s disease,and Alzheimer’s disease.The purinergic P2X4 receptor is an ATP-gated ion channel that is widely expressed in the microglia,astrocytes,and neurons of the central and peripheral nervous systems.P2X4R is involved in the regulation of cellular excitability,synaptic transmission,and neuroinflammation.However,the role played by P2X4R in Parkinson’s disease remains poorly understood.Rat models of Parkinson’s disease were established by injecting 6-hydroxydopamine into the substantia nigra pars compacta.P2X4R-targeted small interfering RNA(siRNA)was injected into the same area 1 week before injury induction to inhibit the expression of the P2X4 receptor.The results showed that the inhibition of P2X4 receptor expression in Parkinson’s disease model rats reduced the rotation behavior induced by apomorphine treatment,increased the latency on the rotarod test,and upregulated the expression of tyrosine hydroxylase,brain-derived neurotrophic factor,LC3-II/LC3-I,Beclin-1,and phosphorylated tropomyosin receptor kinase B(TrkB)in brain tissue,while simultaneously reducing p62 levels.These findings suggest that P2X4 receptor activation might inhibit neuronal autophagy through the regulation of the brain-derived neurotrophic factor/TrkB signaling pathway,leading to dopaminergic neuron damage in the substantia nigra and the further inhibition of P2X4 receptor-mediated autophagy.These results indicate that P2X4 receptor might serve as a potential novel target for the treatment of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Affiliated Hospital of Qingdao University(approval No.QYFYWZLL26119)on April 12,2016.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.
基金This work was supported by the National Natural Science Foundation of China,Nos.81571225 and 81971192(both to AMX).
文摘Dysfunctional autophagy often occurs during the development of neurodegenerative diseases,such as Parkinson’s disease,Huntington’s disease,and Alzheimer’s disease.The purinergic P2X4 receptor is an ATP-gated ion channel that is widely expressed in the microglia,astrocytes,and neurons of the central and peripheral nervous systems.P2X4R is involved in the regulation of cellular excitability,synaptic transmission,and neuroinflammation.However,the role played by P2X4R in Parkinson’s disease remains poorly understood.Rat models of Parkinson’s disease were established by injecting 6-hydroxydopamine into the substantia nigra pars compacta.P2X4R-targeted small interfering RNA(siRNA)was injected into the same area 1 week before injury induction to inhibit the expression of the P2X4 receptor.The results showed that the inhibition of P2X4 receptor expression in Parkinson’s disease model rats reduced the rotation behavior induced by apomorphine treatment,increased the latency on the rotarod test,and upregulated the expression of tyrosine hydroxylase,brain-derived neurotrophic factor,LC3-II/LC3-I,Beclin-1,and phosphorylated tropomyosin receptor kinase B(TrkB)in brain tissue,while simultaneously reducing p62 levels.These findings suggest that P2X4 receptor activation might inhibit neuronal autophagy through the regulation of the brain-derived neurotrophic factor/TrkB signaling pathway,leading to dopaminergic neuron damage in the substantia nigra and the further inhibition of P2X4 receptor-mediated autophagy.These results indicate that P2X4 receptor might serve as a potential novel target for the treatment of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Affiliated Hospital of Qingdao University(approval No.QYFYWZLL26119)on April 12,2016.
