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1.
目的 探讨脂肪酸合成酶(Fatty acid synthase,Fas)基因沉默对帕金森病大鼠脑纹状体多巴胺能神经元凋亡的影响及机制。方法 取40只大鼠,30只大鼠脑纹状体注射4 μL 6-羟基多巴胺(6-Hydroxydopamine Hydrobromide,6-OHDA)建立帕金森病大鼠模型,剩余10只为假手术组,脑纹状体注射等量2 g/L抗坏血酸的生理盐水; 取建模成功的27只大鼠并随机分为模型组、阴性对照组和沉默组,每组各9只; 阴性对照组和沉默组分别向大鼠纹状体内注射3 μL含无义序列的短片断干扰RNA(Small interfer RNA,siRNA)和Fas siRNA,模型组和假手术组分别向大鼠纹状体内注射等量生理盐水; 干预1周后实时荧光定量反转录-聚合酶链反应(Real-time quantitative polymerase chain reaction,RT-qPCR)和Western blot检测大鼠纹状体多巴胺能神经元Fas mRNA和蛋白相对表达水平,苏木精-伊红(hematoxylin eosin,HE)染色观察大鼠纹状体多巴胺能神经元损伤情况,原位末端标记法(TdT-mediated dUTP nick and labeling,TUNEL)染色检测大鼠纹状体多巴胺能神经元凋亡,RT-qPCR,Western blot检测纹状体多巴胺能神经元Fas配体(Fas Ligand,Fasl)、Fas相关死亡结构域蛋白(Fas-associateddeathdomain,FADD)、半胱氨酸天冬氨酸蛋白酶-8(Cysteine containing aspartate-specific proteases-8,Caspase-8)mRNA、蛋白相对表达水平。结果 与假手术组比较,模型组、阴性对照组和沉默组Fas mRNA和蛋白相对表达水平升高(P<0.05); 与模型组和阴性对照组比较,沉默组Fas mRNA和蛋白相对表达水平降低(P<0.05); HE染色显示,Fas基因沉默后神经元排列紊乱程度及胞质肿胀程度减轻,间质较为清晰,空泡皱缩坏死减少; 与假手术组比较,模型组、阴性对照组和沉默组神经元凋亡率升高(P<0.05); 与模型组和阴性对照组比较,沉默组神经元凋亡率降低(P<0.05); 与假手术组比较,模型组、阴性对照组和沉默组Fasl,FADD,Caspase-8 mRNA及蛋白相对表达水平升高(P<0.05); 与模型组比较,沉默组Fasl,FADD,Caspase-8 mRNA及蛋白相对表达水平降低(P<0.05)。结论 Fas基因沉默能抑制帕金森病大鼠脑纹状体多巴胺能神经元凋亡,且可能通过下调Fas,Fasl,FADD,Caspase-8 mRNA及蛋白表达水平来发挥调控作用。  相似文献   
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IntroductionDravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms.Case reportCase 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of 123I–N–ω–fluoropropyl–2β–carbomethoxy–3β–(4–iodophenyl) nortropane (123I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms.DiscussionThe normal DAT SPECT and 123I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.  相似文献   
4.
李欧  张洁  徐建 《陕西中医》2021,(6):687-691,704
目的:探讨香萱益神方治疗血管性痴呆(VD)模型大鼠认知功能作用及其对神经元凋亡机制的研究。方法:两血管阻断法建立VD大鼠模型,给予中药方香萱益神方灌胃治疗6周,分别于造模后、中药喂养6周后进行Morris水迷宫行为学检测,测试大鼠认知行为能力改变,行为学测试结束后,检测VD模型大鼠海马中海马组织脑源性神经营养因子(BDNF)表达水平的变化。结果:香萱益神方治疗6周后,血管性痴呆大鼠模型学习记忆能力得到改善,上调脑内海马组织神经营养因子水平,海马神经元凋亡率下降。结论:香萱益神方是治疗血管性痴呆的有效方剂,可以有效改善VD大鼠模型认知行为功能的障碍情况,起到减少海马神经元细胞凋亡,诱导海马神经元细胞修复的作用。香萱益神方可能是通过激活BDNF相关通路,起到保护海马神经元的作用。  相似文献   
5.
《Molecular therapy》2022,30(4):1465-1483
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In the central nervous system, the type I transmembrane glycoprotein NG2 (nerve-glia antigen 2) is only expressed by pericytes and oligodendrocyte precursor cells (OPCs). Therefore, OPCs are also termed NG2 glia. Their fate during development has been investigated systematically in several genetically modified mouse models. Consensus exists that postnatal NG2 glia are restricted to the oligodendrocyte (OL) lineage, while, at least in the forebrain, embryonic NG2 glia could also generate astrocytes. In addition, experimental evidence for a neurogenic potential of NG2 glia in the early embryonic brain (before E16.5) has been provided. However, this observation is still controversial. Here, we took advantage of reliable transgene expression in NG2-EYFP and NG2-CreERT2 knock-in mice to study the fate of early embryonic NG2 glia. While pericytes were the main cells with robust NG2 gene activity at E12.5, only a few OPCs expressed NG2 at this early stage of embryogenesis. Subsequently, this proportion of OPCs increased from 3% (E12.5) to 11% and 25% at E14.5 and E17.5, respectively. When Cre DNA recombinase activity was induced at E12.5 and E14.5 and pups were analyzed at postnatal day 0 (P0) and P10, the vast majority of recombined cells, besides pericytes, belonged to the OL lineage cells, with few astrocytes in the ventral forebrain. In other brain regions such as brain stem, cerebellum, and olfactory bulb only OL lineage cells were detected. Therefore, we conclude that NG2 glia from early embryonic brain are restricted to a gliogenic fate and do not differentiate into neurons after birth.  相似文献   
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Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.  相似文献   
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PurposeAnimal experiments have shown that the loss of occlusal support causes impairments in spatial cognition. Many reports have focused on the memory encoding process, and only few studies have investigated the effect on memory retrieval. This study aimed to examine the effects of both the loss and reconstruction of occlusal support on the memory retrieval process and on the number of hippocampal pyramidal cells.MethodsThe experimental animals were divided into a molarless group, in which molars were extracted, a denture-wearing molarless group with experimental dentures inserted after molar extraction, and a control group. Radial maze trials were performed for 20 consecutive days (acquisition phase). The rats were tested on long-term memory retention following the acquisition phase in eight trials every five days, and in an additional trial 20 days later (probe phase).ResultsThe denture-wearing molarless group showed higher levels of spatial learning and memory than the molarless group. There were no significant differences in memory retrieval during the probe phase between the denture-wearing molarless and the control group. The molarless group showed significantly worse spatial learning and memory and had fewer neurons in the hippocampus than the control group.ConclusionsOur results suggest that the loss of occlusal support decreases the number of pyramidal cells in the hippocampus and impairs memory decoding and retrieval. However, this effect is suppressed by the reconstruction of occlusal support.  相似文献   
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