共查询到10条相似文献，搜索用时 62 毫秒
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Alpha-synuclein containing cellular inclusions are a hallmark of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. A genome wide expression screen was performed in C. elegans overexpressing both wild-type and A53T human alpha-synuclein. 433 genes were up- and 67 genes down-regulated by statistical and fold change (> or <2) criteria. Gene ontology (GO) categories within the regulated gene lists indicated over-representation of development and reproduction, mitochondria, catalytic activity, and histone groups. Seven genes (pdr-1, ubc-7, pas-5, pas-7, pbs-4, RPT2, PSMD9) with function in the ubiquitin-proteasome system and 35 mitochondrial function genes were up-regulated. Nine genes that form histones H1, H2B, and H4 were down-regulated. These results demonstrate the effects of alpha-synuclein on proteasome and mitochondrial complex gene expression and provide further support for the role of these complexes in mediating neurotoxicity. The results also indicate an effect on nuclear protein genes that suggests a potential new avenue for investigation. 相似文献
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Better understanding of mechanisms of schizophrenia and bipolar disorder: from human gene expression profiles to mouse models 总被引：1，自引：0，他引：1
The molecular mechanisms of major mental illnesses, such as schizophrenia and bipolar disorder, are unclear. To address this fundamental question, many groups have studied molecular expression profiles in postmortem brains and other tissues from patients compared with those from normal controls. Development of unbiased high-throughput approaches, such as microarray, RNA-seq, and proteomics, have supported and facilitated this endeavor. In addition to genes directly involved in neuron/glia signaling, especially those encoding for synaptic proteins, genes for metabolic cascades are differentially expressed in the brains of patients with schizophrenia and bipolar disorder, compared with those from normal controls in DNA microarray studies. Here we propose the importance and usefulness of genetic mouse models in which such differentially expressed molecules are modulated. These animal models allow us to dissect the mechanisms of how such molecular changes in patient brains may play a role in neuronal circuitries and overall behavioral phenotypes. We also point out that models in which the metabolic genes are modified are obviously untested from mental illness viewpoints, suggesting the potential to re-address these models with behavioral assays and neurochemical assessments. 相似文献
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McLean JR Hallett PJ Cooper O Stanley M Isacson O 《Molecular and cellular neurosciences》2012,49(2):230-239
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Greene JG 《Neurobiology of disease》2012,45(1):76-82
Parkinson's disease (PD) is a common age-associated neurodegenerative disorder. Motor symptoms are the cardinal component of PD, but non-motor symptoms, such as dementia, depression, and autonomic dysfunction are being increasingly recognized. Motor symptoms are primarily caused by selective degeneration of substantia nigra dopamine (SNDA) neurons in the midbrain; non-motor symptoms may be referable to well-described pathology at multiple levels of the neuraxis. Development of symptomatic and disease-modifying therapies is dependent on an accurate and comprehensive understanding of the pathogenesis and pathophysiology of PD. Gene expression profiling has been recently employed to assess function on a broad level in the hopes of gaining greater knowledge concerning how individual mechanisms of disease fit together as a whole and to generate novel hypotheses concerning PD pathogenesis, diagnosis, and progression. So far, the majority of studies have been performed on postmortem brain samples from PD patients, but more recently, studies have targeted enriched populations of dopamine neurons and have begun to explore extra-nigral neurons and even peripheral tissues. This review will provide a brief synopsis of gene expression profiling in parkinsonism and its pitfalls to date and propose several potential future directions and uses for the technique. It will focus on the use of microarray experiments to stimulate hypotheses concerning mechanisms of neurodegeneration in PD, since the majority of studies thus far have addressed that complicated issue. 相似文献
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目的 评价不同损毁程度 Ｃ５７ Ｂ Ｌ 小鼠帕金森病（ Ｐ Ｄ）模型纹状体多巴胺转运蛋白（ Ｄ Ａ Ｔ）的变化。方法 根据腹腔注射 Ｍ Ｐ Ｔ Ｐ 的天数将小鼠分为 １、３、５ 和 ７ｄ 模型组以及对照组,静脉注射９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１６ｍ Ｃｉ,１ｈ 后处死行脑纹状体放射自显影,同时行免疫组化酪氨酸羟化酶（ Ｔ Ｈ）染色。结果 对照组的放射自显影可见９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１ 于纹状体部位有高度放射性聚集,且两侧纹状体基本相同。注射 Ｍ Ｐ Ｔ Ｐ １ｄ 者,其纹状体的放射性浓集比对照组有所下降。注射 Ｍ Ｐ Ｔ Ｐ ３、５ 及 ７ｄ 者,两侧纹状体的放射性浓集逐日降低,第 ７ｄ 者几乎消失。 Ｔ Ｈ 染色发现黑质 Ｔ Ｈ 阳性神经元亦随注射 Ｍ Ｐ Ｔ Ｐ 天数的增加而数量减少。结论 不同程度损毁的 Ｃ５７ Ｂ Ｌ 小鼠 Ｐ Ｄ 模型可模拟 Ｐ Ｄ 的发展过程,９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１ 作为 Ｄ Ａ Ｔ 的显影剂可用于早期诊断的神经显像学研究。 相似文献
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目的观察APPswe/PS1ΔE9双转基因小鼠的学习记忆功能及其病理学改变。方法 9月龄雄性APPswe/PS1ΔE9双转基因小鼠和9月龄雄性C57BL/6J小鼠各10只,采用Morris水迷宫检测各组小鼠学习记忆能力情况,并于水迷宫后灌注处死各组小鼠,采用改良Bielschowsky银染法以及尼氏染色法观察小鼠大脑组织病理学变化。结果水迷宫定位航行实验结果显示,APPswe/PS1ΔE9双转基因小鼠的逃避潜伏期与C57对照组小鼠相比明显延长(P<0.05);空间探索实验结果显示,APPswe/PS1ΔE9双转基因小鼠与C57对照组小鼠相比跨台次数减少(P<0.05)。改良Bielschowsky银染法结果显示,C57对照组小鼠大脑皮质未见明显改变,神经原纤维排列有序、稀疏。APPswe/PS1ΔE9双转基因小鼠大脑皮质神经原纤维肿胀,密集成宽带状,可见神经纤维缠结,有老年斑散在分布。尼氏染色结果显示,C57对照组小鼠海马各区神经细胞排列密集、整齐,胞浆中尼氏体丰富,大脑皮质尼氏小体呈深蓝色,细胞核淡蓝色,背景略呈浅蓝色;APPswe/PS1ΔE9双转基因小鼠神经元水肿,细胞数量减少,排列稀疏,细胞间隙增大,胞浆内尼氏体减少,分界不清,染成淡蓝色。结论 APPswe/PS1ΔE9双转基因AD小鼠能够较好的模拟AD患者的表现及病理过程,提供有效的实验动物模型。 相似文献
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Hashimoto M Koda M Ino H Yoshinaga K Murata A Yamazaki M Kojima K Chiba K Mori C Moriya H 《Acta neuropathologica》2005,109(2):165-180
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The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)--a preliminary study using microarray analysis 总被引：3，自引：0，他引：3
Yamaguchi S Kuroda S Kobayashi H Shichinohe H Yano S Hida K Shinpo K Kikuchi S Iwasaki Y 《Brain research》2006,1087(1):15-27
Bone marrow stromal cells (BMSC) have been anticipated as a donor for cell type for transplantation therapy in various neurological disorders. However, their neurogenic capacity still remains undetermined. In this study, we aimed to clarify whether in vitro chemical treatment promotes their neuronal differentiation on the level of gene expression. Mice BMSC were cultured with medium supplemented with DMSO, retinoic acid, and basic fibroblast growth factor, and their morphology and expression of neuronal markers were evaluated. Subsequently, using microarray and RT-PCR techniques, the treatment-induced changes in the gene expression profile were analyzed. After exposure to the medium, the BMSC simulated a neuron-like appearance and increased their immunoreactivity for nestin and Tuj-1. Microarray analysis revealed that the BMSC per se express the multilineage cellular genes, including those associated with the neuron. Chemical treatment significantly decreased the expression of genes related to mesenchymal cells and increased the expression of 5 neuron-associated genes. Microarray and RT-PCR analyses also demonstrated that the BMSC express the genes for several growth factors including NGF-beta and BDNF, indicating their therapeutic role in protecting the injured central nervous system. The present results suggest that at least a certain subpopulation of the BMSC have the potential to alter their gene expression profile in response to the surrounding environment and may possibly protect the host tissue by secreting neuroprotective factors. 相似文献
