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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching
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作者 Jangampalli Adi Pradeepkiran Priyanka Rawat +2 位作者 Arubala P.Reddy Erika Orlov PHemachandra Reddy 《Neural Regeneration Research》 SCIE CAS 2025年第9期2624-2632,共9页
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are... The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition. 展开更多
关键词 diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule
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Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats 被引量:8
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作者 Sheng-min Lai Zi-ting Gu +4 位作者 Meng-meng Zhao Xi-xia Li Yu-xin Ma Li Luo Jing Liu 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第10期1648-1654,共7页
Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity o... Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1:1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats. 展开更多
关键词 nerve regeneration acrylamide hippocampus neurons developmental toxicity growth associated protein 43 synaptophysin weaning rats dentate gyrus protein developmental neurobiology neural regeneration
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AlCl3 exposure regulates neuronal development by modulating DNA modification 被引量:1
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作者 Xue-Jun Cheng Fu-Lai Guan +3 位作者 Qian Li Gong Dai Hai-Feng Li Xue-Kun Li 《World Journal of Stem Cells》 SCIE 2020年第11期1354-1365,共12页
BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive ... BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIM To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.METHODS Neural stem cells were isolated from the forebrain of adult mice.Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice.AlCl3 at 100 and 200μmol/L was applied to stem cells and neurons.RESULTS Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells.Aluminum application also significantly inhibited the dendritic development of hippocampal neurons.Mechanistically,aluminum exposure significantly affected the levels of DNA 5-hydroxy methylcytosine,5-methylcytosine,and N6-methyladenine in stem cells and neurons.CONCLUSION Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications. 展开更多
关键词 ALUMINUM DNA demethylation 5-hydroxymethylcytosine Neural stem cells neuron neuronal development
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Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyelination in the injured spinal cord 被引量:1
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作者 Dan C.Li Qun Li 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第10期1613-1615,共3页
Background and early studies: Endogenous tri-potential neural stem cells (NSCs) exist in the adult mammalian central nervous system (CNS). In the spinal cord, NSCs distribute throughout the entire cord, but exist... Background and early studies: Endogenous tri-potential neural stem cells (NSCs) exist in the adult mammalian central nervous system (CNS). In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts. The phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal. 展开更多
关键词 OPC CNS Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyelination in the injured spinal cord
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Forkhead box protein P1, a key player in neuronal development?
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作者 Luca Braccioli Cora H.Nijboer Paul J.Coffer 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第5期801-802,共2页
Forkhead box protein P1(FOXP1)is a transcription factor belonging to the forkhead box(FOX)proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain(Bacon and Rappold,2... Forkhead box protein P1(FOXP1)is a transcription factor belonging to the forkhead box(FOX)proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain(Bacon and Rappold,2012).Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system(CNS),while mutations in FOXP1 have been implicated in cognitive abnormalities(Bacon and Rappold, 2012). 展开更多
关键词 a key player in neuronal development Forkhead box protein P1
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From neurogenesis to neuronal regeneration: the amphibian olfactory system as a model to visualize neuronal development in vivo
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作者 Ivan Manzini 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第6期872-874,共3页
How do individual neurons develop and how are they in- tegrated into neuronal circuitry? To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult li... How do individual neurons develop and how are they in- tegrated into neuronal circuitry? To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult life. A neural stem cell must go through several stages of maturation, including proliferation, migration, differentiation, and integration, to become fully embedded to an existing neuronal circuit. The knowledge on this topic so far has come mainly from cell culture studies. Studying the development of individual neurons within intact neuronal networks in vivo is inherently difficult. Most neurons are generated form neural stem cells during embryonic and early postnatal development. 展开更多
关键词 the amphibian olfactory system as a model to visualize neuronal development in vivo FIGURE
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Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy
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作者 Chuanjun Liu1, Yue Li2, Huiying Gao3 1Department of Pediatric Internal Medicine, Taian Health Center for Women and Children,Taian 271000, Shandong Province, China 2Department of Anatomy, 3Department of Histology and Embryology, Taishan Medical College, Taian 271000, Shandong Province, China 《Neural Regeneration Research》 SCIE CAS CSCD 2006年第8期681-684,共4页
BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injur... BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system. 展开更多
关键词 Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy
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Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development
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作者 Misako Okumura Takahiro Chihara 《Neural Regeneration Research》 SCIE CAS CSCD 2016年第9期1394-1395,共2页
Basic helix-loop-helix (bHLH) transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the fo... Basic helix-loop-helix (bHLH) transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila (larman et al., 1993, 1994). Atonal is expressed in sensory organ precursors and is required and sufficient for the development of chordotonal organs (Jar- man et al., 1993). Moreover, Atonal expression is observed in the developing eye and is essential for the differentiation of R8 photoreceptors, which are the first photoreceptors that appear during development. Atonal is not involved in the formation of other photoreceptors (R1-R7) directly. However, R8 photore- ceptors recruit other photoreceptors from the surrounding cells (Jarman et al., 1994). 展开更多
关键词 ORN Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development
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Neural Correlates of Developmental Coordination Disorder: The Mirror Neuron System Hypothesis
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作者 Julie M. Werner Sharon A. Cermak Lisa Aziz-Zadeh 《Journal of Behavioral and Brain Science》 2012年第2期258-268,共11页
Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into ad... Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into adulthood, negatively impacting daily life in school, work, and social domains. A better understanding of the neural correlates of motor and imitation impairments in DCD holds the potential for informing development of treatment approaches to address these impairments. Although the disorder is assumed to be of neurological origin, little is known of the brain-based etiology of DCD. In recent years the discovery of a fronto-parietal circuit—known as the mirror neuron system—has enabled researchers to better understand imitation, general motor functions, and aspects of social cognition. Given its involvement in imitation and other motor functions, we propose that dysfunction in the mirror neuron system may underlie the characteristic impairments of DCD. We review literature pertaining to the mirror neuron system and develop a theory of disordered mirror neuron functioning in DCD. Finally, we review the limited neuroimaging literature available on neural correlates of DCD and show that the findings from those investigations are congruent with a mirror neuron system theory of DCD. Future research in this population should be designed to investigate specifically mirror neuron regions in individuals with DCD during skilled motor tasks and imitation in particular. 展开更多
关键词 developmentAL Coordination DISORDER DYSPRAXIA IMITATION Mirror neuron System Motor Learning
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Isoflurane Enhances the Expression of Cytochrome C by Facilitation of NMDA Receptor in Developing Rat Hippocampal Neurons In Vitro 被引量:4
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作者 赵以林 金小高 +3 位作者 王金韬 谭蕾 李世勇 罗爱林 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第6期779-783,共5页
This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (INMDA) and the expression of cytochrome C in cultured developing rat hippocampal neurons... This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (INMDA) and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25, 0.5, 0.75, 1 minimum alveolar concentration (MAC))]. The peak of INMDA was re- corded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane (0.25, 0.5, 0.75 and 1 MAC) potentiated the amplitude of INMDA by (116±8.8)%, (122±11.7)%, (135±14.3)% and (132~14.6)%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P〈0.05). It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor. 展开更多
关键词 inhalation anesthetic ISOFLURANE HIPPOCAMPUS developing neurons calcium NMDA receptor current
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脑发育不同阶段丰富环境刺激对大鼠海马突触素表达的影响 被引量:15
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作者 蒲昭霞 赵聪敏 +1 位作者 李亚伶 张雪琼 《中国儿童保健杂志》 CAS 2007年第6期632-634,共3页
【目的】探讨脑发育不同阶段丰富环境刺激对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生鼠神经可塑性的影响及机制。【方法】7日龄SD大鼠通过结扎左侧颈总动脉,吸入8%氧氮混合气,制成HIBD模型,分为早期干预组、晚期干预... 【目的】探讨脑发育不同阶段丰富环境刺激对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生鼠神经可塑性的影响及机制。【方法】7日龄SD大鼠通过结扎左侧颈总动脉,吸入8%氧氮混合气,制成HIBD模型,分为早期干预组、晚期干预组、非干预组,另设假手术组。早期干预组于脑发育关键期内,即建模后第2 d开始进行丰富环境(environmental enrichment,EE)干预。晚期干预组于脑发育关键期后,即建模后第23 d(日龄30 d)开始进行EE干预。两组干预条件一致,总干预时间为20 d。各组大鼠饲养至日龄100 d时用免疫组织化学法检测患侧海马突触素(synaptophysin,p38)的表达水平。【结果】早期干预组患侧海马p38的表达明显高于晚期干预组和非干预组(P<0.01),早期干预组与假手术组差异无显著性(P>0.05),晚期干预组p38的表达高于非干预组(P<0.05)。【结论】EE干预可增强神经可塑性。p38在海马表达的变化,可能参与了脑发育不同阶段EE对HIBD神经可塑性的影响机制。 展开更多
关键词 缺氧缺血性脑损伤 丰富环境 发育脑 关键期 神经可塑性 突触素
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丙烯酰胺对仔鼠大脑额叶皮质神经元DCX和SYN表达的影响
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作者 李细霞 赵萌萌 +4 位作者 张亚琼 杨德慧 李国营 罗利 刘靖 《神经解剖学杂志》 CAS CSCD 北大核心 2016年第2期205-210,共6页
目的:探究丙烯酰胺(acrylamide,ACR)暴露对仔鼠大脑额叶皮质神经元发育的影响。方法:孕鼠随机分为4组,自怀孕第6 d起对照组和实验组分别给予蒸馏水和(50,100,200)μg/ml ACR饮水,直至仔鼠出生21 d。免疫组织化学法观察仔鼠额叶皮质神经... 目的:探究丙烯酰胺(acrylamide,ACR)暴露对仔鼠大脑额叶皮质神经元发育的影响。方法:孕鼠随机分为4组,自怀孕第6 d起对照组和实验组分别给予蒸馏水和(50,100,200)μg/ml ACR饮水,直至仔鼠出生21 d。免疫组织化学法观察仔鼠额叶皮质神经元微管相关蛋白(doublecortin,DCX)和突触素(synaptophysin,SYN)的表达情况。结果:ACR实验组和对照组额叶皮质神经元均有DCX和SYN的表达。DCX和SYN免疫阳性产物均为棕黄色颗粒状,表达于胞浆内。与对照组相比,ACR染毒高剂量组(200μg/ml)DCX表达显著减少(P<0.05),而低、中剂量组(50μg/ml和100μg/ml)的减少不明显,无统计学意义(P>0.05);与对照组相比,ACR实验组SYN的表达显著降低,呈剂量依赖性,且组间差异明显(P<0.05)。结论:ACR染毒可能是通过降低DCX和SYN的表达,干扰神经元的迁移分化和突触的形成,从而影响额叶皮质的发育。 展开更多
关键词 丙烯酰胺 神经发育毒性 皮质神经元 微管相关蛋白 突触素 大鼠
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miR-34a通过Wnt/β-catenin通路在氯胺酮致发育期大鼠海马神经元凋亡中的作用 被引量:8
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作者 赵晨璐 赵以林 张雪 《郑州大学学报(医学版)》 CAS 北大核心 2021年第1期6-11,共6页
目的:探讨miR-34a在氯胺酮致发育期大鼠海马神经元凋亡中的作用及对Wnt/β-catenin通路的影响。方法:应用生物信息学软件分析预测并通过双荧光素酶报告实验验证miR-34a与Wnt1之间的靶向关系。取7 d龄雄性SD大鼠海马组织,分离培养获得神... 目的:探讨miR-34a在氯胺酮致发育期大鼠海马神经元凋亡中的作用及对Wnt/β-catenin通路的影响。方法:应用生物信息学软件分析预测并通过双荧光素酶报告实验验证miR-34a与Wnt1之间的靶向关系。取7 d龄雄性SD大鼠海马组织,分离培养获得神经元,加0.2 mg/L氯胺酮处理24 h,以未处理细胞为空白对照,采用qRT-PCR检测miR-34a的表达,Annexin V-FITC/PI双染法检测凋亡,Western blot检测Bax、Bcl-2蛋白的表达。另取大鼠海马神经元分为4组,以0.2 mg/L氯胺酮处理24 h后分为4组,miR-NC组、miR-34a组、anti-miR-NC组和anti-miR-34a组,转染48 h后采用Western blot检测Wnt/β-catenin通路相关蛋白Wnt1、β-catenin、TCF-4和Cyclin D1的表达。30只14 d龄SD雄性大鼠随机分为5组,空白对照组、氯胺酮组、anti-miR-NC+si-NC组、anti-miR-34a+si-NC组和anti-miR-34a+si-Wnt1组,每组6只。末次给药24 h后,采用Morris水迷宫实验检测大鼠空间学习能力,qRT-PCR检测miR-34a的表达,TUNEL染色检测大鼠海马神经元凋亡。结果:生物信息学软件分析和双荧光素酶报告实验证实Wnt1和miR-34a有靶向关系。氯胺酮处理会升高海马神经元中miR-34a表达,促进细胞凋亡和Bax的表达,降低Bcl-2的表达(P<0.05)。转染miR-34a模拟物可下调经氯胺酮处理的海马神经元中Wnt/β-catenin信号通路相关蛋白的表达,转染miR-34a抑制剂则可上调该信号通路相关蛋白的表达(P<0.05)。氯胺酮处理会升高SD大鼠海马组织中miR-34a表达,促进细胞凋亡,导致其空间学习能力障碍,miR-34a抑制剂可抑制氯胺酮致大鼠海马组织中细胞凋亡并改善大鼠空间学习能力,下调Wnt1的表达则可减弱miR-34a抑制剂的作用(P<0.05)。结论:miR-34a可促进氯胺酮致发育期大鼠海马神经元凋亡,其机制可能与靶向Wnt1调节Wnt/β-catenin通路有关。 展开更多
关键词 氯胺酮 MIR-34A 细胞凋亡 WNT/Β-CATENIN通路 海马神经元 大鼠 发育期
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脑发育不同阶段丰富环境刺激对大鼠海马MAP-2表达的影响
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作者 蒲昭霞 赵聪敏 张雨平 《重庆医学》 CAS CSCD 北大核心 2009年第22期2790-2792,共3页
目的探讨脑发育不同阶段丰富环境(EE)刺激对缺氧缺血性脑损伤(HIBD)新生鼠神经可塑性的影响及机制。方法7日龄SD大鼠通过结扎左侧颈总动脉,吸入8%氧氮混合气,制成HIBD模型,分为早期干预组、晚期干预组、非干预组,另设假手术组。早期干... 目的探讨脑发育不同阶段丰富环境(EE)刺激对缺氧缺血性脑损伤(HIBD)新生鼠神经可塑性的影响及机制。方法7日龄SD大鼠通过结扎左侧颈总动脉,吸入8%氧氮混合气,制成HIBD模型,分为早期干预组、晚期干预组、非干预组,另设假手术组。早期干预组于脑发育关键期内,即建模后第2天开始进行EE干预。晚期干预组于脑发育关键期后,即建模后第23天(日龄30d)开始进行EE干预。两组干预条件一致,总干预时间为20d。各组大鼠饲养至日龄100d时用免疫组织化学法检测患侧海马微管相关蛋白-2(MAP-2)的表达水平。结果早期干预组患侧海马MAP-2的表达明显高于晚期干预组和非干预组(P<0.01),早期干预组与假手术组差异无统计学意义(P>0.05),晚期干预组MAP-2的表达高于非干预组(P<0.05)。结论EE干预可增强神经可塑性。MAP-2在海马表达的变化,可能参与了脑发育不同阶段EE对HIBD神经可塑性的影响机制。 展开更多
关键词 缺氧缺血性脑损伤 丰富环境 发育脑 关键期 神经可塑性 微管相关蛋白
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NEDD4调控AMPK活性参与心肌细胞慢性缺氧适应的研究 被引量:3
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作者 鞠胜杰 李畑波 +5 位作者 蹇朝 马瑞彦 李经纬 贾维坤 唐富琴 肖颖彬 《第三军医大学学报》 CAS CSCD 北大核心 2015年第9期891-895,共5页
目的探讨NEDD4在心肌细胞慢性缺氧适应过程中的作用及其可能的机制。方法1收集手术矫正的先心病患儿32例,其中紫绀型先心病18例,非紫绀型先心病14例。取术中切除的右室流出道心肌组织作为标本,用免疫组化染色检测NEDD4在心肌细胞中表达... 目的探讨NEDD4在心肌细胞慢性缺氧适应过程中的作用及其可能的机制。方法1收集手术矫正的先心病患儿32例,其中紫绀型先心病18例,非紫绀型先心病14例。取术中切除的右室流出道心肌组织作为标本,用免疫组化染色检测NEDD4在心肌细胞中表达的分布,Western blot检测NEDD4在心肌组织中的表达情况;2将H9c2心肌细胞分为常氧组、慢性缺氧组和阳性对照组,其中慢性缺氧组又分为对照组、空白转染组和干扰转染组,设计合成以心肌细胞NEDD4基因为靶标的siRNA,通过阳离子脂质体将合成的siRNA转染至H9c2心肌细胞中,常氧培养(74%N2,5%CO2,21%O2)48 h后开始对慢性缺氧组心肌细胞进行缺氧刺激(94%N2,5%CO2,1%O2),缺氧刺激72 h后Western blot检测NEDD4、p-AMPK表达水平变化,流式细胞术检测缺氧刺激所致心肌细胞损伤情况。结果 1紫绀组患儿术前血氧饱和度明显低于非紫绀组(P<0.05);免疫组化染色结果显示NEDD4主要分布于心肌细胞质中;与非紫绀组相比,紫绀组患儿心肌组织中NEDD4表达水平显著下降[NEDD4/β-actin条带灰度比值:非紫绀组(0.72±0.07);紫绀组(0.42±0.06),P<0.05];2与常氧组相比,对照组心肌细胞死亡比例显著增加(P<0.05);但干扰NEDD4表达后,缺氧所致心肌细胞损伤比例降低(P<0.05)。Western blot检测结果显示,与空白转染组相比,干扰转染组AMPK磷酸化水平显著增加[p-AMPK/AMPK条带灰度比值:空白转染组(0.21±0.01),干扰转染组(0.88±0.04),P<0.05]。结论 NEDD4可能通过调控AMPK活性参与慢性缺氧情况下心肌细胞代谢的适应调节。 展开更多
关键词 NEDD4 AMPK 慢性缺氧适应
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Glial cells in neuronal development:recent advances and insights from Drosophila melanogaster 被引量:3
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作者 Jiayao Ou Yijing He +4 位作者 Xi Xiao Tian-Ming Yu Changyan Chen Zongbao Gao Margaret S.Ho 《Neuroscience Bulletin》 SCIE CAS CSCD 2014年第4期584-594,共11页
Gila outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passi... Gila outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passive supporting role, are now recognized for their active contributions to almost every aspect of nervous system development. Recently, insights from the invertebrate organism Drosophila melanogaster have advanced our knowledge of glial cell biology. In particular, findings on neuron-glia interactions via intrinsic and extrinsic mechanisms have shed light on the importance of gtia during different stages of neuronal development. Here, we summarize recent advances in understanding the functions of Drosophila glia, which resemble their mammalian counterparts in morphology and function, neural stem-cell conversion, synapse formation, and developmental axon pruning. These discoveries reinforce the idea that glia are substantial players in the developing nervous system and further advance the understanding of mechanisms leading to neurodegeneration. 展开更多
关键词 GLIA neuronal development GCM NEURODEGENERATION neural stem cell synapse formation axon pruning
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The function of DNA topoisomerase IIβ in neuronal development
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作者 衡鑫 乐卫东 《Neuroscience Bulletin》 SCIE CAS CSCD 2010年第5期411-416,共6页
Type II DNA topoisomerases(Tops)are ATP-dependent enzymes that catalyze topological transformations of genomic DNA by the transport of one DNA double helix through another.In mammals,there are 2 isoforms of DNA Top ... Type II DNA topoisomerases(Tops)are ATP-dependent enzymes that catalyze topological transformations of genomic DNA by the transport of one DNA double helix through another.In mammals,there are 2 isoforms of DNA Top II, termed Top IIβ and Top IIβ.The IIβ isoform is abundantly expressed in cells that have undergone the final cell division and are committed to differentiation into neuronal cells.In recent years,there have been accumulating studies showing the significant role of Top IIβ in neuronal development through regulating expression of certain genes in cells committed to the neuronal fate after the final division.These genes are involved in the processes of neuronal differentiation,migration,axon guidance and so on.The present review mainly focused on the research progress on the role of Top IIβ in neuronal development over the recent decades. 展开更多
关键词 neuronal development axon guidance neuronal differentiation
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Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis? 被引量:3
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作者 Zhen Yang Xiao-Gang Yuan +1 位作者 Jiang Chen Nong-Hua Lu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第43期6345-6348,共4页
The expression of phosphatase and tensin homolog (PTEN ), a tumor suppressor gene, is frequently downregulated in gastric carcinomas due to mutation, loss of heterozygosity, and promoter hypermethylation. However, it ... The expression of phosphatase and tensin homolog (PTEN ), a tumor suppressor gene, is frequently downregulated in gastric carcinomas due to mutation, loss of heterozygosity, and promoter hypermethylation. However, it is unknown if additional mechanisms may account for the down-regulation of PTEN expression. While neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) is believed to be a potential dual regulator of PTEN, there are conflicting reports regarding their interaction. To gain further insight into the role of NEDD4-1 and its association with PTEN in gastric carcinoma development, we measured the protein expression of NEDD4-1 and PTEN in gastric mucosae with various pathological lesions and found that NEDD4-1 increased from normal gastric mucosa to intestinal metaplasia and decreased from dysplasia to gastric carcinoma. These changes did not correlate with PTEN expression changes during gastric carcinogenesis. Moreover, we found similar results in protein levels in the primary tumors and adjacent non-tumorous tissues. These results differ from a previous report showing that expression of NEDD4-1 is up-regulated in gastric carcinomas, and show a more complex pattern of NEDD4-1 gene expression during gastric carcinogenesis. 展开更多
关键词 neuronal precursor cell-expressed developmentally down-regulated 4-1 Phosphatase and tensin homolog Gastric carcinogenesis Immunohistochemistry
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The importance of fasciculation and elongation protein zeta-1 in neural circuit establishment and neurological disorders
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作者 Rafhanah Banu Bte Abdul Razar Yinghua Qu +1 位作者 Saravanan Gunaseelan John Jia En Chua 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第6期1165-1171,共7页
The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling network... The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance. 展开更多
关键词 fasciculation and elongation protein zeta-1 neurological disorder neuronal development neuronal differentiation neuronal networks synapse formation synaptic function
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三维神经元几何形态的发育生成方法 被引量:1
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作者 蔺想红 赵吉昌 +1 位作者 李志强 冯丽霞 《计算机工程》 CAS CSCD 北大核心 2017年第10期302-309,共8页
生物神经细胞具有复杂多样的空间几何形态,而这种形态结构是研究单个神经细胞信息处理和整个神经系统连接的基础。为此,提出一种针对三维神经元几何形态的发育生成方法。采用人工基因组对基因调控网络进行编码,用基因表达的动态特性来... 生物神经细胞具有复杂多样的空间几何形态,而这种形态结构是研究单个神经细胞信息处理和整个神经系统连接的基础。为此,提出一种针对三维神经元几何形态的发育生成方法。采用人工基因组对基因调控网络进行编码,用基因表达的动态特性来表示神经元树突树的发育过程。实验结果表明,生成的虚拟神经元与实际神经元具有相似的几何形态结构。与已有基于发育机制的生长方法相比,更真实地表现了生物神经元的发育过程。与基于统计分析的重建方法相比,能够更方便地得到几何形态参数的统计分布函数。 展开更多
关键词 虚拟神经元 神经元形态 基因调控网络 发育机制 参数分析
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