The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t...The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).展开更多
Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upreg...Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.展开更多
BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated pr...BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated protein 43 （GAP-43） and neural cell adhesion molecule following BMSC transplantation to the lateral ventricle in rats with acute focal cerebral ischemic brain damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment using immunohistochemistry was performed at the laboratories of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS PHARMA, Hubei Province, China, from January 2007 to December 2008. MATERIALS： Monoclonal mouse anti-rat 5-bromo-2-deoxyuridine and neural cell adhesion molecule antibodies were purchased from Sigma, USA; monoclonal mouse anti-rat GAP-43 antibody was purchased from Wuhan Boster, China. METHODS： Rat models of right middle cerebral artery occlusion were established using the thread method. At 1 day after middle cerebral artery occlusion, 20μL culture solution, containing 5×10^5 BMSCs, was transplanted to the left lateral ventricle using micro-injection. MAIN OUTCOME MEASURES： Scores of neurological impairment were measured to assess neural function. Expression of GAP-43 and neural cell adhesion molecule at the lesion areas was examined by immunohistochemistry. RESULTS： GAP-43 and neural cell adhesion molecule expression was low in brain tissues of the sham-operated group, but expression increased at the ischemic boundary （P 〈 0.05）. Transplantation of BMSCs further enhanced expression of GAP-43 and neural cell adhesion molecule （P 〈 0.05） and remarkably improved neurological impairment of ischemic rats （P 〈 0.05）. CONCLUSION： BMSC transplantation promoted neurological recovery in rats by upregulating expression of GAP-43 and neural cell adhesion molecule.展开更多
Studies have demonstrated that amyloid precursor protein （APP） expression increases in multiple sclerosis tissues during acutely and chronically active stages. To determine the relationship between axonal injury and...Studies have demonstrated that amyloid precursor protein （APP） expression increases in multiple sclerosis tissues during acutely and chronically active stages. To determine the relationship between axonal injury and regeneration in multiple sclerosis, an animal model of experimental autoimmune encephalomyelitis was induced using different doses of myelin basic protein peptide. APP and growth-associated protein 43 （GAP-43）, which is considered a specific marker of neural regeneration, were assessed by western blot analysis. Expression of APP and GAP-43, as well as the correlation between these two proteins, in brain white matter and spinal cord tissues of experimental autoimmune encephalomyelitis rats at different pathological stages was analyzed. Results showed that APP and GAP-43 expression increased during the acute stage and decreased during remission, with a positive correlation between APP and GAP-43 expression in brain white matter and spinal cord tissues. These results suggest that APP and GAP-43 could provide nutritional and protective effects on damaged neurons.展开更多
This study aimed to explore the pathological change to hippocampal neurons and the expression of growth associated protein 43 in 21-day-old young rats following chronic intermittent hypoxia. Hematoxylin-eosin staining...This study aimed to explore the pathological change to hippocampal neurons and the expression of growth associated protein 43 in 21-day-old young rats following chronic intermittent hypoxia. Hematoxylin-eosin staining results showed varying degrees of degeneration and necrosis in hippocampal neurons depending on the modeling time. Immunohistochemistry revealed that growth associated protein 43 expression in young rats following chronic intermittent hypoxia decreased, but that levels were still higher than those of normal rats at each time point, especially 4 weeks after modeling. During 1 5 weeks after modeling, a slow growth in rat weight was observed. Experimental findings indicate that chronic intermittent hypoxia may induce growth dysfunction and necrosis of hippocampal neurons, as well as increase the expression of growth associated protein 43 in young rats.展开更多
In our previous study, we reported that prenatal restraint stress could induce cognitive deficits, which correlated with a change in expression of growth-associated protein 43 in the hippocampus. In this study, we inv...In our previous study, we reported that prenatal restraint stress could induce cognitive deficits, which correlated with a change in expression of growth-associated protein 43 in the hippocampus. In this study, we investigated the effects of enriched environment on cognitive abilities in prenatally stressed rat offspring, as well as the underlying mechanisms. Reverse transcription-PCR and western blot assay results revealed that growth-associated protein 43 mRNA and protein levels were upregulated on postnatal day 15 in the prenatal restraint stress group. Growth-associated protein 43 expression was significantly lower in the prenatal restraint stress group compared with the negative control and prenatal restraint stress plus enriched environment groups on postnatal days 30 and 50. Morris water maze test demonstrated that cognitive abilities were noticeably increased in rats from the prenatal restraint stress plus enriched environment group on postnatal day 50. These results indicate that enriched environment can improve the spatial learning and memory ability of prenatally stressed offspring by upregulating growth-associated protein 43 expression.展开更多
BACKGROUND： Experimental data indicate that human growth-associated protein 43 mRNA expression coincides with axonal growth during nerve ganglion development; while neurocan, secreted from astrocytes, can inhibit spr...BACKGROUND： Experimental data indicate that human growth-associated protein 43 mRNA expression coincides with axonal growth during nerve ganglion development; while neurocan, secreted from astrocytes, can inhibit sprouting and elongation of the axonal growth cone. OBJECTIVE： To verify regulatory effects of cyclovirobuxine D （CVB-D） extracted from Chinese box branchlet on human growth-associated protein 43 （GAP-43）, and neurocan expression in brain tissue of stroke-prone renovascular hypertensive （RHRSP） rats, at different time points after cerebral ischemia/reperfusion. DESIGN： Randomized grouping design and controlled animal study. SETTING： This study was performed at the Center of Guangdong Hospital of Traditional Chinese Medicine （a national key laboratory） from March 2003 to September 2006. MATERIALS： 100 healthy male Sprague-Dawley rats, aged 2 3 months and weighing 90-120 g, were selected for this study. CVB-D was provided by Nanjing Xiaoying Pharmaceutical Factory （Batch number： 307701）. METHODS： The initial tip of renal arteries was clamped bilaterally for 10 weeks to establish the RHRSP model. 100 RHRSP rats were randomly divided into 4 groups： naive group （n = 10）, sham surgery group （n = 10）, CVB-D group （n = 40）, and lesion group （n = 40）. Rats in the naive group did not undergo any treatment, and cervical vessels of rats in the sham surgery group were exposed, but not blocked. The right middle cerebral artery of rats in the CVB-D group and lesion group were occluded to establish cerebral ischemia. Rats in the CVB-D group were intraperitoneally injected with CVB-D （6.48 mg/kg） every day and with saline （1.5 mL/injection） twice a day. Rats in the lesion group were intraperitoneally injected with saline （2 mL/injection）. MAIN OUTCOME MEASURES： Immunohistochemistry was applied to detect GAP-43 and neurocan expression in the ischemic penumbra region of CVB-D and lesion brains at 2 hours post-cerebral ischemia and at 1, 7, 14, and 30 days post-perfusion （n = 10 at each time point）. Similarly, GAP-43 and neurocan expression was detected in the right hemisphere of naive and sham-operated animals. The results were expressed as positive cells. RESULTS： A total of 100 rats were included in the final analysis. The number of GAP-43 positive cells increased in the CVB-D group 1, 7, 14, and 30 days post-cerebral ischemia/perfusion compared to the lesion group, as indicated by a significant difference between the CVB-D and lesion group （P 〈 0.054）.01）. The number of neurocan-positive cells decreased in the CVB-D group on the first day compared to the model group; however, there was no significant difference between the two groups （P 〉 0.05）. On post-ischemia days 7, 14, and 30, the number of neurocan-positive cells in the CVB-D group was significantly less than in the lesion group （P 〈 0.05）. Both, GAP-43 and neurocan expression was not detectable in brains of naive and sham-operated animals. CONCLUSION： CVB-D treatment up-regulated GAP-43 expression and down-regulated neurocan expression in the ischemic region of RHRSP rats.展开更多
The nuclear-encoded light-harvesting chlorophyll a/b-binding proteins（LHCPs） are specifically translocated from the stroma into the thylakoid membrane through the chloroplast signal recognition particle（cp SRP） pa...The nuclear-encoded light-harvesting chlorophyll a/b-binding proteins（LHCPs） are specifically translocated from the stroma into the thylakoid membrane through the chloroplast signal recognition particle（cp SRP） pathway. The cp SRP is composed of a cp SRP43 protein and a cp SRP54 protein, and it forms a soluble transit complex with LHCP in the chloroplast stroma. Here, we identified the YGL9 gene that is predicted to encode the probable rice cp SRP43 protein from a rice yellow-green leaf mutant. A phylogenetic tree showed that an important conserved protein family, cp SRP43, is present in almost all green photosynthetic organisms such as higher plants and green algae. Sequence analysis showed that YGL9 comprises a chloroplast transit peptide, three chromodomains and four ankyrin repeats, and the chromodomains and ankyrin repeats are probably involved in protein-protein interactions. Subcellular localization showed that YGL9 is localized in the chloroplast. Expression pattern analysis indicated that YGL9 is mainly expressed in green leaf sheaths and leaves. Quantitative real-time PCR analysis showed that the expression levels of genes associated with pigment metabolism, chloroplast development and photosynthesis were distinctly affected in the ygl9 mutant. These results indicated that YGL9 is possibly involved in pigment metabolism, chloroplast development and photosynthesis in rice.展开更多
BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics bloc...BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE： To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS： Thirty-five Spragne Dawley （SD） rats, weighing 200 - 250 g, were randomly divided into four groups： control group （n =5）, simple sciatic nerve transection group （n =10）, peripheral nerve block before and after sciatic nerve transection groups （n =10）. All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods： 3 and 7 days （n =5） respectively. Mouse anti-GAP-43 monoclonal antibody （Sigma Co., Ltd.）, supervision TM anti-mouse reagent （HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai）, and HMIAS-100 image analysis system （Qianping Image Engineering Company, Tongji Medical University） were employed in this study. METHODS： This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE： Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS： All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats （t =8.806, 6.771, P 〈 0.01）. Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats （P 〉 0.05）. CONCLUSION： Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.展开更多
BACKGROUND： The main clinical treatments for optic nerve injury are optic canal decompression and systemic administration of hormones, but both treatments have disadvantages. OBJECTIVE： To observe the pathological c...BACKGROUND： The main clinical treatments for optic nerve injury are optic canal decompression and systemic administration of hormones, but both treatments have disadvantages. OBJECTIVE： To observe the pathological changes in the retina and growth associated protein-43 （GAP-43） expression, to compare the treatment of optic canal decompression, hormones, and their combination with the intracanalicular optic nerve injury.DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the Department of Anatomy, Weifang Medical University, China, from September 2007 to November 2008.MATERIALS： Dexamethasone （Shandong Huaxin Pharmaceutical, China） and rabbit anti-GAP-43 polyclonal antibody （Boster, China） were used.METHODS： All 36 healthy adult rabbits were randomly assigned to control group （n = 4）, simple injury group （n = 20）, and treatment group （n = 12）. Intracanalicular optic nerve injury models were established using the metal cylinder free-fall impact method. The control group was left intact. The treatment group （four rabbits in each subgroup） was treated by optic nerve decompression, dexamethasone treatment （1 mg/kg daily via two intravenous infusions, 1/5 total dose reduction every 3 days, for 14 days）, and simultaneously giving surgery and hormone treatment.MAIN OUTCOME MEASURES： Pathological changes in the retina were determined using hematoxylin-eosin staining. GAP-43 expression was detected using immunohistochemistry in the retina.RESULTS： Retina injury induced obvious pathological changes in the retina. With prolonged time after optic nerve injury, the number of retinal ganglion cells was gradually decreased, and reached the minimum on day 14 （P〈0.01）. All three treatments increased the number of retinal ganglion cells （P〈0.01）, but surgery ＋ hormone treatment was most effective. No GAP-43 cells were present in the normal retinal, but they appeared 3 days after injury, peaked 7 days after injury, and then began to decline.CONCLUSION： Intracanalicular optic nerve injury induced obvious pathological changes in the retina, including increased GAP-43 expression. Optic canal decompression and hormones improved nerve repair after injury, and their combination produced better outcomes.展开更多
An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43...An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43（GAP-43） is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8（SAMP8） mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.展开更多
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).
基金financed by the Spanish"Plan Nacional de Investigación Cientifica,Desorrollo e Innovación Tecnológica,Ministerio de Economíay Competitividod(Instituto de Solud CarlosⅢ)",grant Nos:FIS PI17-0393,FIS PI20-0318co-financed by the"Fondo Europeo de Desorrollo Regional ERDF-FEDER European Union",grant No.P18-RT-5059+2 种基金by"Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020)Consejerio de Transformoción Económico,Industria,Conocimiento y Universidades,Junta de Andolucío,Espa?a",and grant No.A-CTS-498-UGR18by"Programa Operotivo FEDER Andalucía 2014-2020,Universidod de Granada,Junta de Andalucía,Espa?a",ca-funded by ERDF-FEDER,the European Union(all to VC)。
文摘Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.
文摘BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated protein 43 （GAP-43） and neural cell adhesion molecule following BMSC transplantation to the lateral ventricle in rats with acute focal cerebral ischemic brain damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment using immunohistochemistry was performed at the laboratories of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS PHARMA, Hubei Province, China, from January 2007 to December 2008. MATERIALS： Monoclonal mouse anti-rat 5-bromo-2-deoxyuridine and neural cell adhesion molecule antibodies were purchased from Sigma, USA; monoclonal mouse anti-rat GAP-43 antibody was purchased from Wuhan Boster, China. METHODS： Rat models of right middle cerebral artery occlusion were established using the thread method. At 1 day after middle cerebral artery occlusion, 20μL culture solution, containing 5×10^5 BMSCs, was transplanted to the left lateral ventricle using micro-injection. MAIN OUTCOME MEASURES： Scores of neurological impairment were measured to assess neural function. Expression of GAP-43 and neural cell adhesion molecule at the lesion areas was examined by immunohistochemistry. RESULTS： GAP-43 and neural cell adhesion molecule expression was low in brain tissues of the sham-operated group, but expression increased at the ischemic boundary （P 〈 0.05）. Transplantation of BMSCs further enhanced expression of GAP-43 and neural cell adhesion molecule （P 〈 0.05） and remarkably improved neurological impairment of ischemic rats （P 〈 0.05）. CONCLUSION： BMSC transplantation promoted neurological recovery in rats by upregulating expression of GAP-43 and neural cell adhesion molecule.
基金the National Natural Science Foundation of China,No. 30873230Beijing Natural Science Foundation,No. 7092014+1 种基金Scientific Research Common Program of Beijing Municipal Education Commission,No. KM2007100025015Fund-ing Project for Academic Human Resources Devel-opment in Institutions of Higher Learning Under the Jurisdiction of Beijing Mu-nicipality,No. PHR201008401
文摘Studies have demonstrated that amyloid precursor protein （APP） expression increases in multiple sclerosis tissues during acutely and chronically active stages. To determine the relationship between axonal injury and regeneration in multiple sclerosis, an animal model of experimental autoimmune encephalomyelitis was induced using different doses of myelin basic protein peptide. APP and growth-associated protein 43 （GAP-43）, which is considered a specific marker of neural regeneration, were assessed by western blot analysis. Expression of APP and GAP-43, as well as the correlation between these two proteins, in brain white matter and spinal cord tissues of experimental autoimmune encephalomyelitis rats at different pathological stages was analyzed. Results showed that APP and GAP-43 expression increased during the acute stage and decreased during remission, with a positive correlation between APP and GAP-43 expression in brain white matter and spinal cord tissues. These results suggest that APP and GAP-43 could provide nutritional and protective effects on damaged neurons.
基金supported by a grant from Luzhou Medical College,China
文摘This study aimed to explore the pathological change to hippocampal neurons and the expression of growth associated protein 43 in 21-day-old young rats following chronic intermittent hypoxia. Hematoxylin-eosin staining results showed varying degrees of degeneration and necrosis in hippocampal neurons depending on the modeling time. Immunohistochemistry revealed that growth associated protein 43 expression in young rats following chronic intermittent hypoxia decreased, but that levels were still higher than those of normal rats at each time point, especially 4 weeks after modeling. During 1 5 weeks after modeling, a slow growth in rat weight was observed. Experimental findings indicate that chronic intermittent hypoxia may induce growth dysfunction and necrosis of hippocampal neurons, as well as increase the expression of growth associated protein 43 in young rats.
基金supported by a grant from Guangzhou Medical University in China,No. 2010-2012
文摘In our previous study, we reported that prenatal restraint stress could induce cognitive deficits, which correlated with a change in expression of growth-associated protein 43 in the hippocampus. In this study, we investigated the effects of enriched environment on cognitive abilities in prenatally stressed rat offspring, as well as the underlying mechanisms. Reverse transcription-PCR and western blot assay results revealed that growth-associated protein 43 mRNA and protein levels were upregulated on postnatal day 15 in the prenatal restraint stress group. Growth-associated protein 43 expression was significantly lower in the prenatal restraint stress group compared with the negative control and prenatal restraint stress plus enriched environment groups on postnatal days 30 and 50. Morris water maze test demonstrated that cognitive abilities were noticeably increased in rats from the prenatal restraint stress plus enriched environment group on postnatal day 50. These results indicate that enriched environment can improve the spatial learning and memory ability of prenatally stressed offspring by upregulating growth-associated protein 43 expression.
基金the grants from Guangdong Province Administration of Traditional Chinese Medicine, No.103142
文摘BACKGROUND： Experimental data indicate that human growth-associated protein 43 mRNA expression coincides with axonal growth during nerve ganglion development; while neurocan, secreted from astrocytes, can inhibit sprouting and elongation of the axonal growth cone. OBJECTIVE： To verify regulatory effects of cyclovirobuxine D （CVB-D） extracted from Chinese box branchlet on human growth-associated protein 43 （GAP-43）, and neurocan expression in brain tissue of stroke-prone renovascular hypertensive （RHRSP） rats, at different time points after cerebral ischemia/reperfusion. DESIGN： Randomized grouping design and controlled animal study. SETTING： This study was performed at the Center of Guangdong Hospital of Traditional Chinese Medicine （a national key laboratory） from March 2003 to September 2006. MATERIALS： 100 healthy male Sprague-Dawley rats, aged 2 3 months and weighing 90-120 g, were selected for this study. CVB-D was provided by Nanjing Xiaoying Pharmaceutical Factory （Batch number： 307701）. METHODS： The initial tip of renal arteries was clamped bilaterally for 10 weeks to establish the RHRSP model. 100 RHRSP rats were randomly divided into 4 groups： naive group （n = 10）, sham surgery group （n = 10）, CVB-D group （n = 40）, and lesion group （n = 40）. Rats in the naive group did not undergo any treatment, and cervical vessels of rats in the sham surgery group were exposed, but not blocked. The right middle cerebral artery of rats in the CVB-D group and lesion group were occluded to establish cerebral ischemia. Rats in the CVB-D group were intraperitoneally injected with CVB-D （6.48 mg/kg） every day and with saline （1.5 mL/injection） twice a day. Rats in the lesion group were intraperitoneally injected with saline （2 mL/injection）. MAIN OUTCOME MEASURES： Immunohistochemistry was applied to detect GAP-43 and neurocan expression in the ischemic penumbra region of CVB-D and lesion brains at 2 hours post-cerebral ischemia and at 1, 7, 14, and 30 days post-perfusion （n = 10 at each time point）. Similarly, GAP-43 and neurocan expression was detected in the right hemisphere of naive and sham-operated animals. The results were expressed as positive cells. RESULTS： A total of 100 rats were included in the final analysis. The number of GAP-43 positive cells increased in the CVB-D group 1, 7, 14, and 30 days post-cerebral ischemia/perfusion compared to the lesion group, as indicated by a significant difference between the CVB-D and lesion group （P 〈 0.054）.01）. The number of neurocan-positive cells decreased in the CVB-D group on the first day compared to the model group; however, there was no significant difference between the two groups （P 〉 0.05）. On post-ischemia days 7, 14, and 30, the number of neurocan-positive cells in the CVB-D group was significantly less than in the lesion group （P 〈 0.05）. Both, GAP-43 and neurocan expression was not detectable in brains of naive and sham-operated animals. CONCLUSION： CVB-D treatment up-regulated GAP-43 expression and down-regulated neurocan expression in the ischemic region of RHRSP rats.
基金supported by the Special Fund for Industry of Ministry of Agriculture of China (201303129)the Fundamental Research Funds for the Central Universities, China (XDJK2013A023)+1 种基金the Key Program of Chongqing, China (cstc2012ggC 80002)the Upgrade Project of the Key Laboratory of Chongqing, China (cstc2014pt-sy80001)
文摘The nuclear-encoded light-harvesting chlorophyll a/b-binding proteins（LHCPs） are specifically translocated from the stroma into the thylakoid membrane through the chloroplast signal recognition particle（cp SRP） pathway. The cp SRP is composed of a cp SRP43 protein and a cp SRP54 protein, and it forms a soluble transit complex with LHCP in the chloroplast stroma. Here, we identified the YGL9 gene that is predicted to encode the probable rice cp SRP43 protein from a rice yellow-green leaf mutant. A phylogenetic tree showed that an important conserved protein family, cp SRP43, is present in almost all green photosynthetic organisms such as higher plants and green algae. Sequence analysis showed that YGL9 comprises a chloroplast transit peptide, three chromodomains and four ankyrin repeats, and the chromodomains and ankyrin repeats are probably involved in protein-protein interactions. Subcellular localization showed that YGL9 is localized in the chloroplast. Expression pattern analysis indicated that YGL9 is mainly expressed in green leaf sheaths and leaves. Quantitative real-time PCR analysis showed that the expression levels of genes associated with pigment metabolism, chloroplast development and photosynthesis were distinctly affected in the ygl9 mutant. These results indicated that YGL9 is possibly involved in pigment metabolism, chloroplast development and photosynthesis in rice.
基金the Natural Science Foundation of Guangdong Province, No.034628
文摘BACKGROUND： Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 （GAP-43） in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE： To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS： Thirty-five Spragne Dawley （SD） rats, weighing 200 - 250 g, were randomly divided into four groups： control group （n =5）, simple sciatic nerve transection group （n =10）, peripheral nerve block before and after sciatic nerve transection groups （n =10）. All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods： 3 and 7 days （n =5） respectively. Mouse anti-GAP-43 monoclonal antibody （Sigma Co., Ltd.）, supervision TM anti-mouse reagent （HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai）, and HMIAS-100 image analysis system （Qianping Image Engineering Company, Tongji Medical University） were employed in this study. METHODS： This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE： Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS： All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats （t =8.806, 6.771, P 〈 0.01）. Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats （P 〉 0.05）. CONCLUSION： Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.
基金the Educational Commission of Shandong Province of China,No. J06L23
文摘BACKGROUND： The main clinical treatments for optic nerve injury are optic canal decompression and systemic administration of hormones, but both treatments have disadvantages. OBJECTIVE： To observe the pathological changes in the retina and growth associated protein-43 （GAP-43） expression, to compare the treatment of optic canal decompression, hormones, and their combination with the intracanalicular optic nerve injury.DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the Department of Anatomy, Weifang Medical University, China, from September 2007 to November 2008.MATERIALS： Dexamethasone （Shandong Huaxin Pharmaceutical, China） and rabbit anti-GAP-43 polyclonal antibody （Boster, China） were used.METHODS： All 36 healthy adult rabbits were randomly assigned to control group （n = 4）, simple injury group （n = 20）, and treatment group （n = 12）. Intracanalicular optic nerve injury models were established using the metal cylinder free-fall impact method. The control group was left intact. The treatment group （four rabbits in each subgroup） was treated by optic nerve decompression, dexamethasone treatment （1 mg/kg daily via two intravenous infusions, 1/5 total dose reduction every 3 days, for 14 days）, and simultaneously giving surgery and hormone treatment.MAIN OUTCOME MEASURES： Pathological changes in the retina were determined using hematoxylin-eosin staining. GAP-43 expression was detected using immunohistochemistry in the retina.RESULTS： Retina injury induced obvious pathological changes in the retina. With prolonged time after optic nerve injury, the number of retinal ganglion cells was gradually decreased, and reached the minimum on day 14 （P〈0.01）. All three treatments increased the number of retinal ganglion cells （P〈0.01）, but surgery ＋ hormone treatment was most effective. No GAP-43 cells were present in the normal retinal, but they appeared 3 days after injury, peaked 7 days after injury, and then began to decline.CONCLUSION： Intracanalicular optic nerve injury induced obvious pathological changes in the retina, including increased GAP-43 expression. Optic canal decompression and hormones improved nerve repair after injury, and their combination produced better outcomes.
基金supported by a grant from the Health Department of Hebei Province of China,No.20120056,20140314the Funding Project for Introduced Abroad Study Personnel of Hebei Province of China,No.C2011003039
文摘An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43（GAP-43） is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8（SAMP8） mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
