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Phosphorylated low-density lipoprotein receptor-related protein 6 is prevalent in hippocampal progenitor cells and circuits of aged human hippocampus

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Advances in Alzheimer's Disease 2013年第4期2卷 126-131页

作者： Christopher P. Sullivan Rosemary Elliott-Bryant Anish Kanesa-Thasan Ann C. mcKee Richard E. Fine John m. Wells Peter J. morin Department of Biochemistry Boston University School of Medicine Boston USA Department of Neurology Boston University School of Medicine Boston USA Geriatric Research Education and Clinical Center Bedford VA Hospital Bedford USA

Wnt signaling has been implicated in Alzheimer’s disease (AD) pathogenesis, but no studies have described Wnt signaling in aging brain. Phosphorylation of the Wnt coreceptor, low-density lipoprotein receptor-related protein 6 (Lrp6), is a sensitive indicator of Wnt ligand-receptor interaction and canonical Wnt signaling. We report that in aged human temporal lobe, the phospho-Lrp6 (pLrp6) epitope localizes to neurons in the entorhinal cortex (EC), the dentate gyrus (DG), and the hippocampal formation, especially in the CA3 field. Activated Lrp6 is detected in neuronal soma and in neuronal processes, particularly in the mossy fiber terminals in the stratum lucidum of CA3. These three regions and their connectivity represent the afferent arm of the major hippocampal circuit. In the DG, cells positive for pLrp6 include Type 1 and Type 2 hippocampal progenitor cells. Overall, these data indicate regional Wnt receptor activation in the human hippocampus that is most prominent in the cells comprising the afferent arm of the major hippocampal circuit that is associated with learning and memory functions. These findings are consistent with data from rodent studies which suggest an important role for Wnts in adult neurogenesis in the human DG. We speculate that Wnt signaling may be an activity-dependent trophic influence in the hippocampus.

关键词： Wnt LRP6 Hippocampus CA3 Neurogenesis Alzheimer’s

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Transcriptome profiling of 6-OHDA model of Parkinson’s disease

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Advances in Bioscience and Biotechnology 2013年第6期4卷 28-35页

作者： maria I. Shadrina Elena V. Filatova Anelya Kh. Alieva Alla V. Stavrovskaya Rudolph m. Khudoerkov Svetlana A. Limborska Sergei N. Illarioshkin Petr A. Slominsky Institute of molecular Genetics Russian Academy of Sciences Moscow Russia Scientific Centre of Neurology Russian Academy of Medical Sciences Moscow Russia

Analysis of monogenic forms and candidate genes of Parkinson’s disease (PD) does not allow to describe completely the contribution of genetic factors to the etiopathogenesis of the disorder. An approach associated with an analysis of changes in a transcriptome pattern during the development of the disease in model objects can be used to identify new candidate genes that are involved in the pathogenesis of PD. In this work, we performed a transcriptome analysis of a PD model, created via stereotaxic unilateral introduction of the 6-hydroxidopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) of a rat brain, to identify new candidate genes for PD. We studied transcriptome alterations in the substantia nigra of the rat brains 2 weeks after toxin administration, when the rats developed the Parkinson-like phenotype, and 4 weeks after toxin administration, when maximal changes in the behavior of animals were observed. The transcriptome analysis of the substantia nigra of the rat brains at the first time point (2 weeks) revealed changes in expression of genes that were clustered with high significance (p modified Fisher extract p value) into three metabolic pathways according to protein participation: modification of the extracellular matrix, signal transduction (including genes encoding signal peptides), and inflammation processes. This likely indicates that, during this time nonspecific effects associated with the response to surgery took place in the substantia nigra of the rats. Concomitantly, the situation changed dramatically and a response associated with damage to the nervous tissue was observed 4 weeks after neurotoxin administration. As a result, we identified five metabolic pathways containing predominantly genes, that encode protein products that are involved in the processes of neuron projection, normal functioning of the soma and dendrites of neurons, synaptic transmission, and transmission of nerve impulses (p modified Fisher extra

关键词： 6-OHDA Parkinson’s Disease Transcriptome

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P物质和亮-脑啡肽样免疫反应胞体在鼠桥脑被盖背外侧区的不同分布——免疫细胞化学的研究

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湖北医学院学报 1989年第2期10卷 115-119页

作者：周兰仙胡家荤章祖陈管志信湖北医学院人体解剖学教研室

采用PAP免疫细胞化学技术对12只大鼠侨脑被盖背外侧核,蓝斑核和蓝斑下核内含P物质和亮-脑啡肽样免疫反应胞体的分布进行了研究。结果被盖背外侧核和蓝斑核的全长含大量P物质样免疫反应阳性细胞,胞体较大、深染,而亮-脑啡肽样免疫反应神... 详细信息

采用PAP免疫细胞化学技术对12只大鼠侨脑被盖背外侧核,蓝斑核和蓝斑下核内含P物质和亮-脑啡肽样免疫反应胞体的分布进行了研究。结果被盖背外侧核和蓝斑核的全长含大量P物质样免疫反应阳性细胞,胞体较大、深染,而亮-脑啡肽样免疫反应神经元较为稀少,且多集中在核的尾侧区,胞体小,淡染。蓝斑下核内P物质样免疫反应胞体的分布较弥散,而亮-脑啡肽样阳性胞体有成团分布的倾向。表明上述二种肽能神经元在同一脑区的定位存在较大差异。因而有助于阐明同一核群功能的多样性和复杂性。

关键词：脑桥 P物质脑啡肽亮氨酸

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