It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the i...It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a ＂hot spot＂. Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps： keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.展开更多
Objective To investigate the role of porcine small intestinal submucosa (SIS) conduit in axonal regeneration of rat sciatic nerve with a 10 mm gap. Methods Forty-eight rats were randomly divided into three groups (n=1...Objective To investigate the role of porcine small intestinal submucosa (SIS) conduit in axonal regeneration of rat sciatic nerve with a 10 mm gap. Methods Forty-eight rats were randomly divided into three groups (n=16). Following a 10 mm gap was made in one side of the sciatic nerve of each rat; previously prepared SIS and auto-nerve graft were interposed into the gap to reconnect the proximal and distal ends of the nerve, respectively. In the control group, the nerve gap remained unconnected. The samples of the SIS, graft, and distal nerve in group 1 and group 2 were harvested at 6 weeks and 10 weeks after operation, respectively. Axonal regeneration was evaluated by histology, electrophysiology, and quantitated by using computer-analyzed image.Results Regenerative nerve fibers were evident which contained much myelinated axons and grew over the gap in the SIS conduits at 10 weeks. Electrophysiological examination and computer-analyzed image showed that axonal regeneration in the SIS group was similar to that in the auto-nerve grafting group at 10 weeks. Conclusion SIS as a conduit possesses the ability for axonal regeneration of the peripheral nerve, thereby having a potential to be an alternative bio-material instead of the autograft to repair the peripheral nerve gap.展开更多
Peripheral neuropathies refer to a group of conditions in which the peripheral nervous system(PNS)is damaged.These pathological state are are associated with weakness,pain,and loss of motor and sensory control.More th...Peripheral neuropathies refer to a group of conditions in which the peripheral nervous system(PNS)is damaged.These pathological state are are associated with weakness,pain,and loss of motor and sensory control.More than 100 types of peripheral neuropathies have been identified,with distinct symptoms and prognosis classified according to the type of damage to the nerves.Injury to peripheral nerves results in disabling loss of sensory and motor func-展开更多
Since Caenorhabditis elegans was chosen as a model organism by Sydney Brenner in 1960's, genetic studies in this organism have been instrumental in discovering the function of genes and in deciphering molecular si...Since Caenorhabditis elegans was chosen as a model organism by Sydney Brenner in 1960's, genetic studies in this organism have been instrumental in discovering the function of genes and in deciphering molecular signaling network. The small size of the organism and the simple nervous system enable the complete reconstruction of the first connectome. The stereotypic developmental program and the anatomical reproducibility of synaptic connections provide a blueprint to dissect the mechanisms underlying synapse formation. Recent technological innovation using laser surgery of single axons and in vivo imaging has also made C. elegans a new model for axon regeneration. Importantly, genes regulating synaptogenesis and axon regeneration are highly conserved in function across animal phyla. This mini-review will summarize the main approaches and the key findings in understanding the mechanisms underlying the development and maintenance of the nervous system. The impact of such findings underscores the awesome power of C. elegans genetics.展开更多
In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system.Molecular navigational systems c...In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system.Molecular navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth cone.Axon-bound receptors detect these gradients and determine the trajectory of the migrating growth cone.In contrast to their benevolent role in the developing nervous system,repulsive guidance receptors are detrimental to the axon’s ability to regenerate after injury in the adult.In this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor,Ryk/Derailed in axon navigation in the embryonic nervous system(the Yin function).Specifically,we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system,the corticospinal tract and the corpus callosum.Recent studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord injury.Thus,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth(the Yang function).展开更多
Class Ⅲ β-tubulin （Tubb3） is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel...Class Ⅲ β-tubulin （Tubb3） is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel bacterial artificial chromosome （BAC） transgenic mouse line that expresses Class Ⅲ β-tubulin fused to mCherry, an improved monomeric red fluorescent protein, for the visualization of microtubules during neuronal development. A BAC containing Tubb3 gene was modified by insertion of mCherry complementary DNA downstream of Tubb3 coding sequence via homologous recombination, mCherry fusion protein was expressed in the nervous system and testis of the transgenic animal, and the fluorescent signal was observed in the neurons that located in the olfactory bulb, cerebral cortex, hippocampal formation, cerebellum, as well as the retina. Besides, Tubb3-mCherry fusion protein mainly distributed in neurites and colocalized with endogenous Class Ⅲ β-tubulin The fusion protein labels Purkinje cell dendrites during cerebellar circuit formation. Therefore, this transgenic line might be a novel tool for scientific community to study neuronal development both in vitro and in vivo.展开更多
Objective:To study the effect of nerve growth f actor (NGF) and Schwann cells on axon regeneration of the inferior alveolar nerv e following mandibular lengthening with distraction osteogenesis. Methods:Unilateral man...Objective:To study the effect of nerve growth f actor (NGF) and Schwann cells on axon regeneration of the inferior alveolar nerv e following mandibular lengthening with distraction osteogenesis. Methods:Unilateral mandibular osteodistraction was performed i n 9 healthy adult male goats with a distraction rate of 1 mm/d. Every 3 goats we re killed on days 7, 14 and 28 after mandibular lengthening, respectively. The i nferior alveolar nerves in the distraction callus were harvested and processed f or ultrastructural and NGF immunohistochemical study. The inferior alveolar nerv es from the contralateral side were used as controls. Results:On day 7 after distraction, axon degeneration and Schw ann cell proliferation were observed, and very strong staining of NGF in the dis tracted nerve was detected. On day 14 after distraction, axon regeneration and r emyelination were easily observed, and NGF expression started to decline. On day 28 after distraction, the gray scale of NGF immunoreactivity recovered to the n ormal value and the Schwann cells almost recovered to their normal state. Conclusions:Gradual mandibular osteodistraction can result in mild or moderate axon degeneration of the inferior alveolar nerve. Nerve trauma may stimulate the proliferation of Schwann cells and promote the synthesis and s ecretion of NGF in the Schwann cells. Schwann cells and NGF might play important roles in axon regeneration of the injured inferior alveolar nerve following man dibular lengthening.展开更多
Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods: Twenty-four rat...Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods: Twenty-four rats were divided into experimental and control groups, each group having 12 rats. The spinal cord injury was established by transecting the spinal cord at T 10 level with microsurgery scissors. OECs were purified from SD rat olfactory bulb and cultured in DMEM (Dulbeccos minimum essential medium) and cryopreserved (-120℃) for two weeks. OECs suspension [(1-1.4)×10 5/ul] was transplanted into transected spinal cord, while the DMEM solution was injected instead in the control group. At 6 and 12 weeks after transplantation, the rats were evaluated with climbing test and MEP (moter evoked potentials) monitoring. The samples of spinal cord were procured and studied with histological and immunohisto chemical stainings. Results: At 6 weeks after transplantation, all of the rats in both transplanted and control groups were paraplegic, and MEPs could not be recorded. Morphology of transplanted OECs was normal, and OECs were interfused with host well. Axons could regrow into gap tissue between the spinal cords. Both OECs and regrown axons were immunoreactive for MBP. No regrown axons were found in the control group. At 12 weeks after transplantation, 2 rats (2/7) had lower extremities muscle contraction, 2 rats (2/7) had hip and/or knee active movement, and MEP of 5 rats (5/7) could be recorded in the calf in the transplantation group. None of the rats (7/7) in the control group had functional improvement, and none had MEPs recorded. In the transplanted group, histological and immunohistochemical methods showed the number of transplanted OECs reduced and some regrown axons had reached the end of transected spinal cord. However, no regrown axons could be seen except scar formation in the control group. Conclusions: Cryopreserved OECs could integrated with the host and promote regrowing axons across the transected spinal cord ends.展开更多
Erratum to:SCIENCE CHINA Life Sciences,November 2015 Vol.58 No.11:1084–1088doi:10.1007/s11427-015-4962-9In the first paragraph of the manuscript,the name of Charles Harrington was printed in error,should be Charles S...Erratum to:SCIENCE CHINA Life Sciences,November 2015 Vol.58 No.11:1084–1088doi:10.1007/s11427-015-4962-9In the first paragraph of the manuscript,the name of Charles Harrington was printed in error,should be Charles Sherrington.展开更多
Reproduction in fish is controlled by the brain-pituitary-gonad reproductive axis. Although genes of the reproductive axis are conserved from fish to humans, their in vivo functions are less clear in fish. Mutant line...Reproduction in fish is controlled by the brain-pituitary-gonad reproductive axis. Although genes of the reproductive axis are conserved from fish to humans, their in vivo functions are less clear in fish. Mutant lines of the reproductive axis have been systematically investigated in zebrafish and medaka using recently developed genome-editing nucleases. Here, we review recent progress in the genetic analysis of the reproductive axis in fish as well as the opportunities and challenges of applying genome-editing nucleases in fisheries.展开更多
基金supported by the National Natural Science Foundation of China(No.30571909,No.30872666)the Youth Teacher Foundation of Jiangsu Pro-vince(No.BU134701)China,and the Medical Development Foundation of Soochow University(No.EE134615)
文摘It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a ＂hot spot＂. Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps： keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.
基金National Natural Science Foundation of China (30371444).
文摘Objective To investigate the role of porcine small intestinal submucosa (SIS) conduit in axonal regeneration of rat sciatic nerve with a 10 mm gap. Methods Forty-eight rats were randomly divided into three groups (n=16). Following a 10 mm gap was made in one side of the sciatic nerve of each rat; previously prepared SIS and auto-nerve graft were interposed into the gap to reconnect the proximal and distal ends of the nerve, respectively. In the control group, the nerve gap remained unconnected. The samples of the SIS, graft, and distal nerve in group 1 and group 2 were harvested at 6 weeks and 10 weeks after operation, respectively. Axonal regeneration was evaluated by histology, electrophysiology, and quantitated by using computer-analyzed image.Results Regenerative nerve fibers were evident which contained much myelinated axons and grew over the gap in the SIS conduits at 10 weeks. Electrophysiological examination and computer-analyzed image showed that axonal regeneration in the SIS group was similar to that in the auto-nerve grafting group at 10 weeks. Conclusion SIS as a conduit possesses the ability for axonal regeneration of the peripheral nerve, thereby having a potential to be an alternative bio-material instead of the autograft to repair the peripheral nerve gap.
基金funded by FONDAP program 15150012(to CH and FAC)Millennium Institute,No.P09-015-F+12 种基金the Frick Foundation 20014-15ALS Therapy Alliance 2014-F-059Muscular Dystrophy Association 382453CONICYT-USA 2013-0003Michael J Fox Foundation for Parkinson′s Research–Target Validation grant No.9277COPEC-UC Foundation 2013.R.40Ecos-Conicyt C13S02FONDECYT No.1140549Office of Naval Research-Global(ONR-G)N62909-16-1-2003ALSRP Therapeutic Idea Award AL150111(to CH)Millennium Nucleus-P-07-011-FFONDECYT,No.1110987(to FAC)PhD fellow supported by CONICYT,No.21130843(to MO)
文摘Peripheral neuropathies refer to a group of conditions in which the peripheral nervous system(PNS)is damaged.These pathological state are are associated with weakness,pain,and loss of motor and sensory control.More than 100 types of peripheral neuropathies have been identified,with distinct symptoms and prognosis classified according to the type of damage to the nerves.Injury to peripheral nerves results in disabling loss of sensory and motor func-
基金support from the National Institute of Healththe Howard Hughes Medical Institute of the United States of America
文摘Since Caenorhabditis elegans was chosen as a model organism by Sydney Brenner in 1960's, genetic studies in this organism have been instrumental in discovering the function of genes and in deciphering molecular signaling network. The small size of the organism and the simple nervous system enable the complete reconstruction of the first connectome. The stereotypic developmental program and the anatomical reproducibility of synaptic connections provide a blueprint to dissect the mechanisms underlying synapse formation. Recent technological innovation using laser surgery of single axons and in vivo imaging has also made C. elegans a new model for axon regeneration. Importantly, genes regulating synaptogenesis and axon regeneration are highly conserved in function across animal phyla. This mini-review will summarize the main approaches and the key findings in understanding the mechanisms underlying the development and maintenance of the nervous system. The impact of such findings underscores the awesome power of C. elegans genetics.
基金supported by an Australian Postgraduate Awardthe Queensland Government’s National and International Research Alliances Program and the National Health and Medical Research Council of Australia for financial support(456040,569638,1010723)+2 种基金the National Natural Science Foundation of China(81330026,31271259,30990261,30871425)the National Basic Research Program,Ministry of Science and Technology of China(2013CB945604)the Chinese Academy of Sciences(KSCX2-EW-Q-11)for funding support
文摘In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system.Molecular navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth cone.Axon-bound receptors detect these gradients and determine the trajectory of the migrating growth cone.In contrast to their benevolent role in the developing nervous system,repulsive guidance receptors are detrimental to the axon’s ability to regenerate after injury in the adult.In this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor,Ryk/Derailed in axon navigation in the embryonic nervous system(the Yin function).Specifically,we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system,the corticospinal tract and the corpus callosum.Recent studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord injury.Thus,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth(the Yang function).
文摘Class Ⅲ β-tubulin （Tubb3） is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel bacterial artificial chromosome （BAC） transgenic mouse line that expresses Class Ⅲ β-tubulin fused to mCherry, an improved monomeric red fluorescent protein, for the visualization of microtubules during neuronal development. A BAC containing Tubb3 gene was modified by insertion of mCherry complementary DNA downstream of Tubb3 coding sequence via homologous recombination, mCherry fusion protein was expressed in the nervous system and testis of the transgenic animal, and the fluorescent signal was observed in the neurons that located in the olfactory bulb, cerebral cortex, hippocampal formation, cerebellum, as well as the retina. Besides, Tubb3-mCherry fusion protein mainly distributed in neurites and colocalized with endogenous Class Ⅲ β-tubulin The fusion protein labels Purkinje cell dendrites during cerebellar circuit formation. Therefore, this transgenic line might be a novel tool for scientific community to study neuronal development both in vitro and in vivo.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No .3 9970 797)
文摘Objective:To study the effect of nerve growth f actor (NGF) and Schwann cells on axon regeneration of the inferior alveolar nerv e following mandibular lengthening with distraction osteogenesis. Methods:Unilateral mandibular osteodistraction was performed i n 9 healthy adult male goats with a distraction rate of 1 mm/d. Every 3 goats we re killed on days 7, 14 and 28 after mandibular lengthening, respectively. The i nferior alveolar nerves in the distraction callus were harvested and processed f or ultrastructural and NGF immunohistochemical study. The inferior alveolar nerv es from the contralateral side were used as controls. Results:On day 7 after distraction, axon degeneration and Schw ann cell proliferation were observed, and very strong staining of NGF in the dis tracted nerve was detected. On day 14 after distraction, axon regeneration and r emyelination were easily observed, and NGF expression started to decline. On day 28 after distraction, the gray scale of NGF immunoreactivity recovered to the n ormal value and the Schwann cells almost recovered to their normal state. Conclusions:Gradual mandibular osteodistraction can result in mild or moderate axon degeneration of the inferior alveolar nerve. Nerve trauma may stimulate the proliferation of Schwann cells and promote the synthesis and s ecretion of NGF in the Schwann cells. Schwann cells and NGF might play important roles in axon regeneration of the injured inferior alveolar nerve following man dibular lengthening.
文摘Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods: Twenty-four rats were divided into experimental and control groups, each group having 12 rats. The spinal cord injury was established by transecting the spinal cord at T 10 level with microsurgery scissors. OECs were purified from SD rat olfactory bulb and cultured in DMEM (Dulbeccos minimum essential medium) and cryopreserved (-120℃) for two weeks. OECs suspension [(1-1.4)×10 5/ul] was transplanted into transected spinal cord, while the DMEM solution was injected instead in the control group. At 6 and 12 weeks after transplantation, the rats were evaluated with climbing test and MEP (moter evoked potentials) monitoring. The samples of spinal cord were procured and studied with histological and immunohisto chemical stainings. Results: At 6 weeks after transplantation, all of the rats in both transplanted and control groups were paraplegic, and MEPs could not be recorded. Morphology of transplanted OECs was normal, and OECs were interfused with host well. Axons could regrow into gap tissue between the spinal cords. Both OECs and regrown axons were immunoreactive for MBP. No regrown axons were found in the control group. At 12 weeks after transplantation, 2 rats (2/7) had lower extremities muscle contraction, 2 rats (2/7) had hip and/or knee active movement, and MEP of 5 rats (5/7) could be recorded in the calf in the transplantation group. None of the rats (7/7) in the control group had functional improvement, and none had MEPs recorded. In the transplanted group, histological and immunohistochemical methods showed the number of transplanted OECs reduced and some regrown axons had reached the end of transected spinal cord. However, no regrown axons could be seen except scar formation in the control group. Conclusions: Cryopreserved OECs could integrated with the host and promote regrowing axons across the transected spinal cord ends.
文摘Erratum to:SCIENCE CHINA Life Sciences,November 2015 Vol.58 No.11:1084–1088doi:10.1007/s11427-015-4962-9In the first paragraph of the manuscript,the name of Charles Harrington was printed in error,should be Charles Sherrington.
文摘Reproduction in fish is controlled by the brain-pituitary-gonad reproductive axis. Although genes of the reproductive axis are conserved from fish to humans, their in vivo functions are less clear in fish. Mutant lines of the reproductive axis have been systematically investigated in zebrafish and medaka using recently developed genome-editing nucleases. Here, we review recent progress in the genetic analysis of the reproductive axis in fish as well as the opportunities and challenges of applying genome-editing nucleases in fisheries.
