共查询到19条相似文献,搜索用时 156 毫秒
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用电穿孔法将大鼠酷氨酸羟化酶(Tyrosine hydroxylase,TH)基因转染大鼠L6TG成肌细胞株,经PCR检测、免疫组织化学和荧光组织化学检测证明,TH基因能在细胞内稳定整合和表达,并在辅因子存在时将酷氨酸转化为多巴,移植于大鼠纹状体后可成活并表达TH。 相似文献
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大鼠延髓至下丘脑腹内侧核的儿茶酚胺能投射神经元在胃伤害性刺激后的Fos表达 总被引:1,自引:0,他引:1
本实验用HRP注入下丘脑腹内侧核结合逆行追踪与抗FOS蛋白和抗酪氨酸羟化酶(TH)抗血清双重免疫细胞化学相结合的三重标记方法,对大鼠孤束核和延髓腹外侧区至下丘脑腹内侧核的儿茶酚胺能投射神经元在胃伤害性刺激后的c-fos表达进行了观察。本文发现孤束核和延髓腹外侧区有七种不同的标记细胞:HRP、Fos、TH单标细胞Fos/HRP、Fos/TH、HRP/TH双标细胞和Fos/HRP/TH三标细胞。上述七种标记细胞主要分布在延髓中段和尾段孤束核的内侧亚核和延髓腹外侧区以及两者之间的网状结构。HRP标记细胞以注射侧为主,对侧有少量分布。本文结果证明,大鼠孤束核、延髓腹外侧区和网状结构内儿茶酚胺能神经元有些至下丘脑腹内侧核的投射,其中一部分儿茶酚胺能神经元参与了胃伤害性刺激的传导和调控。 相似文献
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Itwasrecentlyevidencedthatmetabolicdisturbancesoffolicacidarecloselyrelatedtocardiovasculardiseasesandbirthdefects.5,10MTHFRisanimportantenzymeinthefolicacidmetabolicsystem.DecreaseinMTHFRactivitymayinducetheappearanceofhyperhomocysteinemia,whichmaycaus… 相似文献
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α—氯代醇对雄性大鼠的不育效果研究 总被引:18,自引:0,他引:18
α氯代醇对雄性大鼠的不育效果研究THESTERILEEFFECTSOFALPHACHLOROHYDRINONMALERATS关键词α氯代醇不育剂大鼠KeywordsAlphachlorohydrin,Sterilant,Rat采取灌胃法和隔一... 相似文献
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树突状细胞 (Dendriticcells ,DC)是体内功能最强的抗原提呈细胞 ,它们的表面表达主要组织相容性复合物 (MajorHistocompatibilityComplex ,MHC)分子和共刺激分子 ,为淋巴细胞的活化提供双信号。DC活化后分泌IL - 12、IL - 18及干扰素等细胞因子刺激辅助型T细胞 (HelperTcells ,TH)增殖 ,促使TH0 和TH2 细胞向TH1细胞分化 ,并强烈激发TH1型免疫应答[1] ,从而增强机体的抗肿瘤、抗感染、自身免疫性疾病和移植排斥等细胞免疫反应。应用DC的抗肿瘤实验主要是… 相似文献
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黄嘴白鹭的繁殖生物学 总被引:3,自引:0,他引:3
黄嘴白鹭的繁殖生物学THEBREEDINGBIOLOGYOFTHECHINESEEGRET关键词黄嘴白鹭繁殖生长率恒温能力发育食物组成KeywordsChineseegret,Breeding,Growthrate,Developmentofhome... 相似文献
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用成年大鼠75只,给右侧黑质区注射6-羟基多巴胺(6-OHDA),损毁黑质多巴胺能神经元,制备偏侧帕金森氏病(PD)鼠模型。四周后,注射阿朴吗啡(APO)诱发大鼠向左侧旋转。旋转数为每分钟7次以上的35只PD鼠作实验用。其中实验组15只,对照组20只。向实验组PD鼠右侧纹状体多点植入含大鼠酪氨酸羟化酶cDNA(THcDNA)的真核表达载体pSVK3-TH和脂质体Lipofectin混合的基因转染复 相似文献
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Xia CF Chu C Li J Wang Y Zhang Y Boado RJ Pardridge WM 《The journal of gene medicine》2007,9(7):605-612
BACKGROUND: The present study examines whether chromosomal derived forms of therapeutic genes can be delivered to brain following intravenous administration. The brain expression of a rat tyrosine hydroxylase (TH) cDNA is compared to the brain expression of a plasmid DNA encoding the 18 kb rat TH gene. METHODS: TH gene expression is measured in cell culture and in vivo in brain in experimental Parkinson's disease (PD). A total of four eukaryotic expression plasmids encoding rat TH were engineered wherein the size of the TH expression cassette ranged from 1.5 kb, in the case of the cDNA form of the gene, to 17.5 kb, in the case of the largest size genomic construct. The TH expression plasmids were delivered to either cultured cells or to rat brain in vivo with Trojan horse liposomes (THLs), which target the non-viral plasmid DNA to cells via cell membrane receptors. RESULTS: The pattern of TH gene expression in cell culture and in vivo was similar: the cDNA form of the TH gene was fast-acting with short duration of action, and the genomic form of the TH gene was slow-acting with longer duration of action. The most sustained replacement of striatal TH enzyme activity in experimental PD was produced by combination gene therapy where both the cDNA and the genomic forms of the TH gene were administered simultaneously. CONCLUSIONS: Eukaryotic expression plasmids encoding genomic forms of therapeutic genes, as large as 18 kb, can be successfully incorporated in THLs and delivered to brain following intravenous administration. 相似文献
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永生化胶质细胞介导TH基因的长效基因治疗 总被引:3,自引:0,他引:3
胶质细胞是脑部疾病基因治疗中的理想载体细胞 ,但细胞来源有限 ,体外培养时间短等因素限制了原代胶质细胞在基因治疗中的应用。以SV4 0大T抗原转化原代大鼠原代胶质细胞得到的永生化胶质细胞 (RGLT)可解决这些问题。在成瘤性检测中 ,RGLT细胞在裸鼠皮下 (观察 4周 )和大鼠纹状体内 (观察 18个月 )均不能成瘤。将大鼠酪氨酸羟化酶 (TH)基因转入RGLT细胞得到RGLT TH细胞后 ,TH免疫组化和HPLC检测表明RGLT TH细胞可表达TH并在体外合成多巴胺。将RGLT TH细胞移值入 6 羟基多巴胺损毁的帕金森病 (PD)大鼠模型的纹状体后 ,可大幅提高纹状体内多巴胺含量并显著缓解PD症状 ,疗效稳定维持超过 18个月。这些结果表明永生化胶质细胞可以安全有效地用于神经退行性疾病的长效基因治疗。 相似文献
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Takashi Iwakura Miyuki Sakoh Atsuhiro Tsutiya Naoya Yamashita Akiko Ohtani Mumeko C. Tsuda Sonoko Ogawa Shinji Tsukahara Masugi Nishihara Takashi Shiga Yoshio Goshima Tomohiro Kato Ritsuko Ohtani‐Kaneko 《Developmental neurobiology》2013,73(7):502-517
In the sexually dimorphic anteroventral periventricular nucleus (AVPV) of the hypothalamus, females have a greater number of tyrosine hydroxylase‐immunoreactive (TH‐ir) and kisspeptin‐immunoreactive (kisspeptin‐ir) neurons than males. In this study, we used proteomics analysis and gene‐deficient mice to identify proteins that regulate the number of TH‐ir and kisspeptin‐ir neurons in the AVPV. Analysis of protein expressions in the rat AVPV on postnatal day 1 (PD1; the early phase of sex differentiation) using two‐dimensional fluorescence difference gel electrophoresis followed by MALDI‐TOF‐MS identified collapsin response mediator protein 4 (CRMP4) as a protein exhibiting sexually dimorphic expression. Interestingly, this sexually differential expressions of CRMP4 protein and mRNA in the AVPV was not detected on PD6. Prenatal testosterone exposure canceled the sexual difference in the expression of Crmp4 mRNA in the rat AVPV. Next, we used CRMP4‐knockout (CRMP4‐KO) mice to determine the in vivo function of CRMP4 in the AVPV. Crmp4 knockout did not change the number of kisspeptin‐ir neurons in the adult AVPV in either sex. However, the number of TH‐ir neurons was increased in the AVPV of adult female CRMP4‐KO mice as compared with the adult female wild‐type mice. During development, no significant difference in the number of TH‐ir neurons was detected between sexes or genotypes on embryonic day 15, but a female‐specific increase in TH‐ir neurons was observed in CRMP4‐KO mice on PD1, when the sex difference was not yet apparent in wild‐type mice. These results indicate that CRMP4 regulates the number of TH‐ir cell number in the female AVPV. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 502–517, 2013 相似文献
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人羊膜上皮细胞移植及基因治疗帕金森病大鼠 总被引:3,自引:0,他引:3
观察人羊膜上皮细胞(human amniotic epithelial cell,HAEC及)人脑源性神经营养因子(brain-derived neurotrophic factor,BDNF基)因修饰的HAEC在帕金森病(Parkinson’sdisease,PD)模型大鼠脑内的长期存活和对旋转行为的治疗效果。用包装BDNFcDNA的慢病毒转染原代HAEC(HAEC/BDNF),HAEC/BDNF与HAEC分别植入6-羟基多巴胺损伤的PD模型大鼠纹状体内,观察动物的旋转行为,用免疫组织化学方法鉴定移植物在体内的存活。结果表明,治疗组PD大鼠的旋转行为改善明显达14周,HAEC/BDNF组能使恢复时间提前。免疫组织化学方法发现移植细胞在14周后仍有少量存活且部分表达BDNF、酪氨酸羟化酶,纹状体内星形胶质细胞增生。实验结果说明,HAEC和BDNF基因修饰的HAEC移植对PD模型大鼠的行为有一定改善,HAEC可以作为一种治疗PD的供体细胞。 相似文献
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Tanya Chotibut Richard W. Davis Jennifer C. Arnold Zachary Frenchek Shawn Gurwara Vimala Bondada James W. Geddes Michael F. Salvatore 《Molecular neurobiology》2014,49(3):1282-1292
Excess glutamatergic neurotransmission may contribute to excitotoxic loss of nigrostriatal neurons in Parkinson's disease (PD). Here, we determined if increasing glutamate uptake could reduce the extent of tyrosine hydroxylase (TH) loss in PD progression. The beta-lactam antibiotic, ceftriaxone, increases the expression of glutamate transporter 1 (GLT-1), a glutamate transporter that plays a major role in glutamate clearance in central nervous system and may attenuate adverse behavioral or neurobiological function in other neurodegenerative disease models. In association with >80 % TH loss, we observed a significant decrease in glutamate uptake in the established 6-hydroxydopamine (6-OHDA) PD model. Ceftriaxone (200 mg/kg, i.p.) increased striatal glutamate uptake with >5 consecutive days of injection in nonlesioned rats and lasted out to 14 days postinjection, a time beyond that required for 6-OHDA to produce >70 % TH loss (~9 days). When ceftriaxone was given at the time of 6-OHDA, TH loss was ~57 % compared to ~85 % in temporally matched vehicle-injected controls and amphetamine-induced rotation was reduced about 2-fold. This attenuation of TH loss was associated with increased glutamate uptake, increased GLT-1 expression, and reduced Serine 19 TH phosphorylation, a calcium-dependent target specific for nigrostriatal neurons. These results reveal that glutamate uptake can be targeted in a PD model, decrease the rate of TH loss in a calcium-dependent manner, and attenuate locomotor behavior associated with 6-OHDA lesion. Given that detection of reliable PD markers will eventually be employed in susceptible populations, our results give credence to the possibility that increasing glutamate uptake may prolong the time period before locomotor impairment occurs. 相似文献
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Jin GZ Cho SJ Choi EG Lee YS Yu XF Choi KS Yee ST Jeon JT Kim MO Kong IK 《Cell biology international》2008,32(11):1433-1438
Mesenchymal stem cells (MSCs) are pluripotent adult stem cells. It has been shown that MSCs secrete neurotrophic factors involving nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Also, these neurotrophic factors can upregulate tyrosine hydroxylase (TH) gene expression in PC12 cells and neural stem cells. Here, we investigated the effect of co-culturing rat E13.5 ventral mesencephalic cells (VMCs) with MSCs from rat bone marrow on TH expression and dopamine (DA) content. The study consisted of 3 groups: MSC, VMC and a combined MSC+VMC group. All groups were cultured in serum-free neuro-basal medium for 3 days. Thereafter, each group was analyzed by RT-PCR, western blotting, and HPLC. The co-culture group showed a higher expression at TH and DA than the VMC group. However, TH and DA were not present in the MSC group. These observations suggest that MSCs could be an alternative source for treating neurodegenerative diseases such as Parkinson's disease (PD). 相似文献