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Mitochondrial protective and anti-apoptotic effects of Rhodiola crenulata extract on hippocampal neurons in a rat model of Alzheimer's disease

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Neural Regeneration Research 2017年第12期12卷 2025-2034页

作者： Jun-mei Wang Ze-qiang Qu Jin-lang Wu Peter Chung yuan-shan zeng Department of Histology and Embryology Zhongshan School of Medicine Sun Yat-sen University Guangzhou Guangdong Province China Department of Electron Microscope Zhongshan School of Medicine Sun Yat-sen University Guangzhou Guangdong Province China shanghai Ninth People's Hospital Shanghai liao Tong University School of Medicine Shanghai China Institute of Spinal Cord In)ury Sun Yat-sen University Guangzhou Guangdong Province China Co-innovation Center of Neuroregeneration Nantong University Nantong Jiangsu Province China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-sen University Guangzhou Guangdong Province China

In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata（RCE） improved spatial cognition in a rat model of Alzheimer＇s disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression. However, the mechanisms underlying the neuroprotective effects of RCE are unclear. In the present study, we investigated the anti-apoptotic effect of RCE and its neuroprotective mechanism of action in a rat model of Alzheimer＇s disease established by intracerebroventricular injection of streptozotocin. The rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days before model establishment. ATP and cytochrome c oxidase levels were significantly decreased in rats with Alzheimer＇s disease. Furthermore, neuronal injury was obvious in the hippocampus, with the presence of a large number of apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and cytochrome c oxidase levels were markedly increased, the number of apoptotic neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of RCE had the optimal effect. These findings suggest that pretreatment with RCE prevents mitochondrial dysfunction and protects hippocampal neurons from apoptosis in rats with Alzheimer＇s disease.

关键词： nerve regeneration Alzheimer's disease intracerebroventricular injection streptozotocin neuronal apoptosis neuroprotection cytochrome c oxidase adenosine triphosphate caspase-3 NeuN neural regeneration

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Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord

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Neural Regeneration Research 2021年第11期16卷 2276-2283页

作者： Yu-Rong Bai Bi-Qin Lai Wei-Tao Han Jia-Hui Sun Ge Li Ying Ding Xiang zeng yuan-Huan Ma yuan-shan zeng Key Laboratory for Stem Cells and Tissue Engineering Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Histology and Embryology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Institute of Spinal Cord Injury Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord ***,achieving good outcome remains *** previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion ***,it has not been reported whether this material promotes axonal regeneration in *** the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann *** functional scaffold promoted the directional growth and remyelination of regenerating *** vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel *** spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem *** scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin ***,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in *** weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were ***,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin *** procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval ***-IACUC-2019-B034)on February 28,2019.

关键词： axonal regeneration decellularized optic nerve directional regeneration functional scaffold microenvironment neurotrophin-3 optic nerve remyelination Schwann cells tissue engineering white matter injury

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Improvement in acupoint selection for acupuncture of nerves surrounding the injury site: electro-acupuncture with Governor vessel with local meridian acupoints

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Neural Regeneration Research 2015年第1期10卷 128-135页

作者： Guan-heng He Jing-wen Ruan yuan-shan zeng Xin Zhou Ying Ding Guang-hui Zhou Department of Acupuncture the First Affiliated HospitalSun Yat-sen University Division of Neuroscience Department of Histology and EmbryologyZhongshan School of MedicineSun Yat-sen University Rehabilitation Department People’s Hospital of Dongguan ShilongSouthern Medical University

Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apop- tosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined （GV/LM group） with acupuncture at local meridian acupoints alone （LM group） in the treatment of patients with peripheral nerve injury. In the GV/LM group （n = 15）, in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated： Baihui （GV20）, Fengfu （GV16）, Dazhui （GV14）, and Shenzhu （GV12）, selected to treat nerve injury of the upper limb, and Jizhong （GV6）, Mingmen （GV4）, Yaoyangguan （GV3）, and Yaoshu （GV2） to treat nerve injury of the lower limb. In the LM group （n = 15）, only me- ridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/ LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduc- tion tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacu- puncture in one patient with rad

关键词： nerve regeneration peripheral nerve injury acupuncture electroacupuncture Governorvessel acupoints local acupoints eleetrophysiology spinal cord motor nerve conduction functionalrepair neural regeneration

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Synergistic Effect of Schwann Cells and Retinoic Acid on Differentiation and Synaptogenesis of Hippocampal Neural Stem Cells in vitro

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Biomedical and Environmental Sciences 2006年第3期19卷 219-224页

作者： XUE-BAO ZHANG yuan-shan zeng WEI ZHANG YA-YUN CHEN YI XIONG SUI-JUN CHEN Division of Neuroscience Department of Histology and Embryology Zhongshan Medical College Sun Yat-Sen University Guangzhou 510080 Guangdong China

Objective To investigate the synergistic effect of Schwann cells （SCs） and retinoic acid （R.A） on differentiation and synaptogenesis of neural stem cells （NSCs） derived from hippocampus of neonatal rats. Methods The classical method for 2×2 factorial analysis experiment was used to assess synergistic action of SCs and RA. NSCs were treated with R.A, SCs, and SCs ＋ RA in DMEM/F12 with 0.5% fetal bovine serum for six days, respectively. Double immunofluorescent staining was used to detect the differentiation of NSCs including nestin, glial fibrillary acidic protein （GFAP） and Map2. The expression of PSD95 was used to demonstrate synaptogenesis. Results After NSCs were treated with RA or SCs, the expression of nestin and GFAP was significantly decreased while the expression of Map2 and PSD95 was significantly increased in comparison with the control. Factorial ANOVA showed that interactions between SCs and RA could induce the expression of Map2 and PSD95. Conclusion SCs and RA could promote synergistically the neuronal differentiation and synaptogenesis of hippocampal neural stem cells in vitro while they decreased the astrocytes and nestin positive NSCs.

关键词： Neural stem cell Neuronal differentiation PSD95 Schwann cells Retinoic acid

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Construction of a niche-specific spinal white matter-like tissue to promote directional axon regeneration and myelination for rat spinal cord injury repair

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Bioactive Materials 2022年第5期7卷 15-31页

作者： Bi-Qin Lai Yu-Rong Bai Wei-Tao Han Bao Zhang Shu Liu Jia-Hui Sun Jia-Lin Liu Ge Li Xiang zeng Ying Ding yuan-Huan Ma Ling Zhang Zheng-Hong Chen Jun Wang yuan Xiong Jin-Hua Wu Qi Quan Ling-Yan Xing Hong-Bo Zhang yuan-shan zeng Key Laboratory for Stem Cells and Tissue Engineering(Sun Yat-sen University) Ministry of EducationGuangzhou510080China Department of Histology and Embryology Zhongshan School of MedicineSunYat-sen UniversityGuangzhou510080China Institute of Spinal Cord Injury Sun Yat-sen UniversityGuangzhou510120China Co-innovation Center of Neuroregeneration Nantong UniversityNantong226001China Department of Anatomy Anhui Medical UniversityHefei230032China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou510080China Department of Geriatrics The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China Physiotherapy Department Guangdong Work Injury Rehabilitation HospitalGuangzhouChina Department of Orthopedic Surgery Key Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing Key Lab of Regenerative Medicine in OrthopedicsThe 4th Medical CentreChinese PLA General HospitalBeijingChina

Directional axon regeneration and remyelination are crucial for repair of spinal cord injury(SCI),but existing treatments do not effectively promote those ***,we propose a strategy for construction of niche-specific spinal white matter-like tissue(WMLT)using decellularized optic nerve(DON)loaded with neurotrophin-3(NT-3)-overexpressing oligodendrocyte precursor cells.A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was *** WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control *** transplants integrated well with host spinal cord white matter,effectively addressing several barriers to directional axonal regeneration and myelination during SCI *** WMLT,laminin was found to promote development of oligodendroglial lineage(OL)cells by binding to laminin ***,laminin could also guide linear axon regeneration via interactions with specific integrins on the axon *** WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin,NT-3 and OL cells to achieve significant structural repair of *** protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.

关键词： Extracellular matrix Oligodendroglial lineage cells White matter-like tissue Directional axon regeneration Spinal cord injury

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A promising avenue using stem cell based exogenous neuronal relay for repairing rat spinal cord transection injury

A promising avenue using stem cell based exogenous neuronal ...

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中国神经科学学会第十二届全国学术会议

作者： Bi-Qin Lai Xiang zeng yuan-shan zeng Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University) Ministry of Education Department of Histology and Embryology Zhongshan School of Medicine Sun Yat-sen University

Objective To generate a tissue-engineered neural network in vitro and to investigate whether this network grafted could enhance the formation of an anatomical and functional neuronal relay in conduction neural signals crossing the completely transected rat spinal cord. Methods Co-culture of neurotrophin-3（NT-3） gene-modified Schwann cells（SCs, NT-3-SCs） and Trk C（NT-3 receptor） gene-modified neural stem cells（NSCs, Trk C-NSCs） in a gelatin sponge scaffold to construct a tissue-engineered neural network. The exogenous neural network was transplanted into rat with T10 segment of the spinal cord removed. The effect of NT-3 on the synaptogenesis of Trk C gene-modified NSCs was examined. Results A NSC-derived neural network with synaptic transmission was successfully constructed in vitro. Further study showed that NT-3/Trk C interactions activated the PI3 K/Akt/m TOR pathway and PI3 K/Akt/CREB pathway facilitating synaptogenesis of NSC-derived neurons residing in the scaffold in vitro. Eight weeks after transplantation, a favorable microenvironment for axonal regeneration and for survival and synaptogenesis of NSC-derived neurons was examined. Cholera toxin B subunit（b-CTB, a transneuronal tracer） was utilized as retrograde labeling reagent via sciatic nerve injection to laminate the host neurons and grafted NSCderived neurons in the spinal cord. Remarkably, not only ascending and descending nerve fibers, but also propriospinal neurons, made contacts with b-CTB positive NSC-derived neurons. Moreover, b-CTB positive exogenous NSC-derived neurons extended their axons to make contacts with the motor neurons located in the caudal area to the injury/graft site. Furthermore, a part of these connections was confirmed to be synapses by double-labeled immunoelectron microscopy. Animals with neural network scaffold transplantation resulted in higher BBB score besides the improved cortical motor evoked potentials. Conclusion The present findings suggest that NT-3-mediated Trk C sig

关键词： Neurotrophin-3 Synaptogenesis Tissue engineering neural network Neuronal relay Spinal cord injury

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An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury

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Bioactive Materials 2021年第11期6卷 3766-3781页

作者： Ge Li Bao Zhang Jia-hui Sun Li-yang Shi Meng-yao Huang Li-jun Huang Zi-jing Lin Qiong-yu Lin Bi-qin Lai yuan-huan Ma Bin Jiang Ying Ding Hong-bo Zhang Miao-xin Li Ping Zhu Ya-qiong Wang Xiang zeng yuan-shan zeng Key Laboratory for Stem Cells and Tissue Engineering Ministry of EducationSun Yat-sen UniversityGuangzhou510080China Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong510100China Department of Histology and Embryology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou510080China Institute of Spinal Cord Injury Sun Yat-sen UniversityGuangzhou510120China State Key Laboratory of Chemo/Biosensing and Chemometrics College of BiologyHunan UniversityChangsha410082China Co-innovation Center of Neuroregeneration Nantong UniversityNantong226001China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou510080China Laboratory of Precision Medical Genomics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou510080China Department of Electron Microscope Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou510080China

The mechanism underlying neurogenesis during embryonic spinal cord development involves a specific ligand/receptor interaction,which may be help guide neuroengineering to boost stem cell-based neural regeneration for the structural and functional repair of spinal cord ***,we hypothesized that supplying spinal cord defects with an exogenous neural network in the NT-3/fibroin-coated gelatin sponge(NF-GS)scaffold might improve tissue repair *** test this,we engineered tropomyosin receptor kinase C(TrkC)-modified neural stem cell(NSC)-derived neural network tissue with robust viability within an NF-GS *** NSCs were genetically modified to overexpress TrkC,the NT-3 receptor,a functional neuronal population dominated the neural network *** pro-regenerative niche allowed the long-term survival and phenotypic maintenance of the donor neural network tissue for up to 8 weeks in the injured spinal ***,host nerve fibers regenerated into the graft,making synaptic connections with the donor ***,motor function recovery was significantly improved in rats with spinal cord injury(SCI)that received TrkC-modified NSC-derived neural network tissue ***,the results suggested that transplantation of the neural network tissue formed in the 3D bioactive scaffold may represent a valuable approach to study and develop therapies for SCI.

关键词： Neurotrophin-3 Tropomyosin kinase receptor C Self-organization Neural network tissue Spinal cord injury

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Transplantation of NT-3 delivery acellular optic nerve scaffold to improve motor function in transected rat spinal cord

Transplantation of NT-3 delivery acellular optic nerve scaff...

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中国神经科学学会第十二届全国学术会议

作者： Ge Li Jia-Hui Sun yuan-shan zeng Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University) Ministry of Education Department of Histology and Embryology Zhongshan School of Medicine Sun Yat-sen University

Objective To generate a bioactive scaffold with line-shaped tubes in vitro and investigate whether the scaffold transplanted into the injury site could promote nerve fiber regeneration and functional recovery in rat spinal cord transected completely. Methods By using aseptic decellular, DNAase hydrolysis and freeze-drying techniques, natural optic nerve was removed all cell component and coated with neurotrophin-3（NT-3）/fibroin complex at the surface to fabricate a NT-3 delivery acellular optic nerve scaffold. Then, dorsal root ganglion（DRG） was seeded on the surface of NT-3 delivery acellular optic nerve scaffold in vitro to observe the effect of the scaffold on DRG neurite growth, and the scaffold were transplanted into the injury site of spinal cord injury of rat. Results Fresh normal optic nerve of longitudinal section was stained by HE showing high-density tubes with optic nerve fibers. By using aseptic decellular technique and freeze-drying technique, the NT-3 delivery acellular optic nerve scaffold still maintained its natural 3 dimension（3 D） structure of extracellular matrix. Circle-shaped pipelines made of perineurium-like extracellular matrix in optic nerve of transverse section could be obseved and there were line-shaped tubes with interconnections in optic nerve of longitudinal section after all cell component was removed. These results were further conformed under a scanning electron microscope. The present study proved that cell component had been removed by the results below;*** nuclei were invisible by Hoechst33342 staining. 2. DNA electrophoresis showed that residual DNA fragments were less than 200 bp. 3. DNA quantification showed ＜ 50 ng per mg scaffold dry weight. Therefore, cells seeded in the scaffold could grow without nucleic acid residue effect. Then, after DRG was seeded on the scaffold in vitro, we found that DRG derived NF200 positive neurites could grow a long distance in the surface of the scaffold. Furthermore, two months later aft

关键词： Neutrophin-3 delivery Acellular optic nerve Neurite growth Nerve fiber regeneration Spinal cord injury

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预先服用灵芝孢子降低维甲酸诱导的孕鼠胚胎神经管畸形发生率

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中西医结合学报 2006年第4期4卷 368-373页

作者：张伟曾园山熊轶陈穗君钟志强中山大学中山医学院组织胚胎学教研室神经科学研究室广东广州510080

目的探讨预先服用灵芝孢子能否降低维甲酸诱导的胚胎神经管畸形的发生率。方法将胚胎(embryo,E)0d孕鼠随机分为正常对照组、溶剂组、模型组和灵芝孢子组,每组5只。灵芝孢子组孕鼠于E0d起即给予胃饲灵芝孢子溶液,溶剂组孕鼠胃饲等量溶剂... 详细信息

目的探讨预先服用灵芝孢子能否降低维甲酸诱导的胚胎神经管畸形的发生率。方法将胚胎(embryo,E)0d孕鼠随机分为正常对照组、溶剂组、模型组和灵芝孢子组,每组5只。灵芝孢子组孕鼠于E0d起即给予胃饲灵芝孢子溶液,溶剂组孕鼠胃饲等量溶剂。至E7.75d时,模型组和灵芝孢子组孕鼠一次性胃饲全反式维甲酸。E10.5d时取孕鼠胚胎,计算神经管畸形发生率及测量胚胎顶臀距。采用免疫荧光组织化学染色和流式细胞术检测胚胎神经管神经上皮细胞巢蛋白的表达及细胞周期分布,采用DNA定量荧光染色及RT-PCR技术检测胚胎神经管细胞周期素依赖性蛋白激酶2(cyclin-dependentkinase2,Cdk2)和Cdk4mRNA的转录水平。结果孕鼠胚胎神经管畸形发生率模型组为79.41%,灵芝孢子组为21.67%;顶臀距模型组为(3.62±1.27)mm,灵芝孢子组为(5.84±0.92)mm。胚胎神经管神经上皮细胞巢蛋白表达阳性率模型组为32.44%,灵芝孢子组为77.65%。模型组孕鼠胚胎神经管神经上皮细胞G0/G1期比例为82.80%,灵芝孢子组为53.74%。灵芝孢子组Cdk4mRNA转录水平高于正常对照组和溶剂组,但未检测到Cdk2mRNA。结论预先服用灵芝孢子能够降低维甲酸诱导的孕鼠胚胎神经管畸形的发生率。

关键词：神经管畸形灵芝孢子维甲酸巢蛋白细胞周期素依赖性蛋白激酶

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基于改进AHP与集对分析法的防空兵群阵地选择

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指挥控制与仿真 2008年第3期30卷 39-41,57页

作者：张天文袁山增防空兵指挥学院河南郑州450052

防空兵群阵地选择是防空兵力部署的前提条件,阵地选择与配置的正确与否是防空兵部队能否有效进行抗击敌空袭兵器的一个重要因素。在分析以往防空阵地优选方法不足的基础上,提出了基于改进的层次分析与集对分析的多因素优选方法,建立了... 详细信息

防空兵群阵地选择是防空兵力部署的前提条件,阵地选择与配置的正确与否是防空兵部队能否有效进行抗击敌空袭兵器的一个重要因素。在分析以往防空阵地优选方法不足的基础上,提出了基于改进的层次分析与集对分析的多因素优选方法,建立了防空兵群配置地域方案优选的模型。通过实例分析了影响防空兵群阵地选择的相关因素,确定了配置地域优选的指标体系,用三标度法确定指标因素的权重,以相对贴近度的大小对待选阵地进行优选和排序。该方法能够定性与定量相结合,模型简单规范,为防空兵群阵地优选提供了一种有效的方法和途径。

关键词：防空兵群阵地选择集对分析三标度法

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