In this paper, we present a simulation program that allows for the concurrent propagation of action potentials in axons coupled via currents, as well as, for the first time, the computation of the resultant nodal elec...In this paper, we present a simulation program that allows for the concurrent propagation of action potentials in axons coupled via currents, as well as, for the first time, the computation of the resultant nodal electric field generated as the action potentials traverse the tract of axons. With these fields in hand, we inject currents into nodes of axons that depend on these fields and study the coupling between axons in the presence of the fields and currents present jointly in varying strengths. We find close-to-synchronized propagation in three dimensions. Further, we derive for the first time a mathematical equation for tortuous tracts (as opposed to linear) with such field-mediated coupling. The geometrical formulation enables us to consider spacetime perturbative effects, which have also not been considered in the literature so far. We investigate the case when gravitational radiation is present, in order to determine its impact on tract information processing. We find that action potential relative-timing in a tract is affected by the strength and frequency of gravitational waves and the waning of this influence with weakening strength. This latter study blurs the division between what lies inside and outside man. As an additional novelty, we investigate the influence of geometry on the information transmission capacity of the ephaptically-coupled tract, when viewed as a discrete memoryless channel, and find a rising trend in capacity with increasing axonal inclinations, which may occur in traumatic CNS injury.展开更多
Axonal injury is a pathological hallmark of both head injury and inflammatory-mediated neurological disorders,including multiple sclerosis（Schirmer et al.,2013）.Such axonal disruptions and/or disconnections typicall...Axonal injury is a pathological hallmark of both head injury and inflammatory-mediated neurological disorders,including multiple sclerosis（Schirmer et al.,2013）.Such axonal disruptions and/or disconnections typically result in proximal axonal segments that remain in continuity with the neuronal somawhile losing contact with their distal targets.展开更多
Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cell...Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.展开更多
c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-in...c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.展开更多
The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates thr...The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cel...Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels.Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver.However,the role of platelet in the liver metastatic niche of PDAC remains elusive.This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC.Methods:An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC.Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis.Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1(Ephb1),tumor cell-platelet adhesion,recombinant protein,and tryptophan hydroxylase 1(Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche.Results:The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients.Platelet depletion decreased liver metastatic tumor growth in mice.Mechanistically,tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1(EFNB1)mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation,and in turn,activated platelet-released 5-HT,further enhancing tumor growth.Conclusion:We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC.Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver.Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.展开更多
Axons in central nervous system （CNS） do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord iniury. Both intrinsic and extrinsic factors are responsible for the regeneration fail- u...Axons in central nervous system （CNS） do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord iniury. Both intrinsic and extrinsic factors are responsible for the regeneration fail- ure, Although intensive research efforts have been invested on extrinsic regeneration inhibitors, the extent to which glial inhibitors contribute to the regeneration failure in viva still remains elusive. Recent exper- imental evidence has rekindled interests in intrinsic factors for the regulation of regeneration capacity in adult mammals. In this review, we propose that activating macrophages with pro-regenerative molecular signatures could be a novel approach for boosting intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model in which regeneration of central branches of dorsal root ganglia sensory neu- rons is enhanced by a preceding injury to the peripheral branches, we have demonstrated that perineuronal macrophages surrounding dorsal root ganglia neurons are critically involved in the maintenance of en- hanced regeneration capacity. Neuron-derived chemokine （C-C motif） ligand 2 （CCL2） seems to mediate neuron-macrophage interactions conveying injury signals to perineuronal macrophages taking on a soley pro-regenerative phenotype, which we designate as regeneration-associated macrophages （RAMs）. Ma- nipulation of the CCL2 signaling could boost regeneration potential mimicking the conditioning injury, suggesting that the chemokine-mediated RAM activation could be utilized as a regenerative therapeutic strategy for CNS injuries.展开更多
Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord ...Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.展开更多
文摘In this paper, we present a simulation program that allows for the concurrent propagation of action potentials in axons coupled via currents, as well as, for the first time, the computation of the resultant nodal electric field generated as the action potentials traverse the tract of axons. With these fields in hand, we inject currents into nodes of axons that depend on these fields and study the coupling between axons in the presence of the fields and currents present jointly in varying strengths. We find close-to-synchronized propagation in three dimensions. Further, we derive for the first time a mathematical equation for tortuous tracts (as opposed to linear) with such field-mediated coupling. The geometrical formulation enables us to consider spacetime perturbative effects, which have also not been considered in the literature so far. We investigate the case when gravitational radiation is present, in order to determine its impact on tract information processing. We find that action potential relative-timing in a tract is affected by the strength and frequency of gravitational waves and the waning of this influence with weakening strength. This latter study blurs the division between what lies inside and outside man. As an additional novelty, we investigate the influence of geometry on the information transmission capacity of the ephaptically-coupled tract, when viewed as a discrete memoryless channel, and find a rising trend in capacity with increasing axonal inclinations, which may occur in traumatic CNS injury.
基金the center of the current manuscript was performed as a component of the Operation Brain Trauma Therapy consortium,which is supported by U.S.Army grants W81XWH-10-1-0623 and WH81XWH-14-2-0018Microscopy was performed at the VCU Department of Anatomy and Neurobiology Microscopy Facility,supported,in part,with funding from NIH-NINDS Center core grant 5P30NS047463
文摘Axonal injury is a pathological hallmark of both head injury and inflammatory-mediated neurological disorders,including multiple sclerosis（Schirmer et al.,2013）.Such axonal disruptions and/or disconnections typically result in proximal axonal segments that remain in continuity with the neuronal somawhile losing contact with their distal targets.
基金This work was also supported by the National Natural Science Foundation of China,No.81901365(to WRQ)Jilin Science and Technology Agency Funds in China,Nos.20180101118JC(to RL),20180520115JH(to BPC)and 20190103076JH(to WRQ).
文摘Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.
基金supported by the Henan Province Education Department Key Project of Science and Technology Research in China,No.12A350006
文摘c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.
基金supported by an Australian Postgraduate Award to D.A
文摘The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金Natural Science Foundation of Shanghai,Grant/Award Number:22ZR1460000Shanghai Municipal Health Commission,Grant/Award Number:202340202+1 种基金National Natural Science Foundation of China,Grant/Award Numbers:82073023,82103357,82173153,82230087,82273228,82303278,82350123,82372821,92168111Innovative research team of high-level local universities in Shanghai,Grant/Award Number:SHSMU-ZDCX20210802。
文摘Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels.Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver.However,the role of platelet in the liver metastatic niche of PDAC remains elusive.This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC.Methods:An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC.Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis.Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1(Ephb1),tumor cell-platelet adhesion,recombinant protein,and tryptophan hydroxylase 1(Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche.Results:The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients.Platelet depletion decreased liver metastatic tumor growth in mice.Mechanistically,tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1(EFNB1)mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation,and in turn,activated platelet-released 5-HT,further enhancing tumor growth.Conclusion:We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC.Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver.Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.
文摘Axons in central nervous system （CNS） do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord iniury. Both intrinsic and extrinsic factors are responsible for the regeneration fail- ure, Although intensive research efforts have been invested on extrinsic regeneration inhibitors, the extent to which glial inhibitors contribute to the regeneration failure in viva still remains elusive. Recent exper- imental evidence has rekindled interests in intrinsic factors for the regulation of regeneration capacity in adult mammals. In this review, we propose that activating macrophages with pro-regenerative molecular signatures could be a novel approach for boosting intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model in which regeneration of central branches of dorsal root ganglia sensory neu- rons is enhanced by a preceding injury to the peripheral branches, we have demonstrated that perineuronal macrophages surrounding dorsal root ganglia neurons are critically involved in the maintenance of en- hanced regeneration capacity. Neuron-derived chemokine （C-C motif） ligand 2 （CCL2） seems to mediate neuron-macrophage interactions conveying injury signals to perineuronal macrophages taking on a soley pro-regenerative phenotype, which we designate as regeneration-associated macrophages （RAMs）. Ma- nipulation of the CCL2 signaling could boost regeneration potential mimicking the conditioning injury, suggesting that the chemokine-mediated RAM activation could be utilized as a regenerative therapeutic strategy for CNS injuries.
基金supported by the State Key Program of National Natural Science Foundation of China,No.81330042(to SQF)the International Cooperation Program of the National Natural Science Foundation of China,No.81620108018(to SQF)
文摘Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.
