Parkinson’s disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain α-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to α-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in α-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression.
The specialized epithelium covering the lymphoid follicles of Peyer's patches in the gut mediates transcytosis of antigens to the underlying immune cells, mainly through the membranous, or M, cells. At present, the molecular processes involved in the mucosal immune response, and in antigen transport across the follicle-associated epithelium (FAE) and M cells, are poorly understood. To characterize FAE and M cells, we compared the gene expression profiles of small intestine FAE and villus epithelium (VE) in BALB/c mice by microarray analysis; 91 genes were found to be up-regulated and four down-regulated at least two-fold (p<0.01) in the FAE. The differential expression of a subset of these genes was shown to be confirmed by quantitative RT-PCR. Using immunohistochemistry on BALB/c Peyer's patches, cathepsin H and clusterin expression was increased in the FAE compared to the VE. Moreover, we demonstrated M cell-specific expression of annexin V, which has recently been reported to be important in endocytic transport and membrane scaffolding, suggesting that annexin V has a function in M cell-mediated transcytosis.
Olfactory dysfunction is common in Parkinson’s disease. Zapiec et al. devise a rigorous quantitative approach to describe the glomerular component of the entire human olfactory bulb. The global glomerular voxel volume in Parkinson's disease is half that of controls, with differences seen predominantly in the ventral olfactory bulb.
The organization of proteins in space and time is essential to their function. To accurately quantify subcellular protein characteristics in a population of cells with regard for the stochasticity of events in a natural context, there is a fast-growing need for image-based cytometry. Simultaneously, the massive amount of data that is generated by image-cytometric analyses, calls for tools that enable pattern recognition and automated classification. In this article, we present a general approach for multivariate phenotypic profiling of individual cell nuclei and quantification of subnuclear spots using automated fluorescence mosaic microscopy, optimized image processing tools, and supervised classification. We demonstrate the efficiency of our analysis by determination of differential DNA damage repair patterns in response to genotoxic stress and radiation, and we show the potential of data mining in pinpointing specific phenotypes after transient transfection. The presented approach allowed for systematic analysis of subnuclear features in large image data sets and accurate classification of phenotypes at the level of the single cell. Consequently, this type of nuclear fingerprinting shows potential for high-throughput applications, such as functional protein assays or drug compound screening. ' 2009 International Society for Advancement of Cytometry
Reduced olfactory function (hyposmia) is one of the most common non-motor symptoms experienced by those living with Parkinson's disease (PD), however, the underlying pathology of the dysfunction is unclear. Recent evidence indicates that α-synuclein (α-syn) pathology accumulates in the anterior olfactory nucleus of the olfactory bulb years before the motor symptoms are present. it is well established that neuronal cells in the olfactory bulb are affected by α-syn, but the involvement of other non-neuronal cell types is unknown. the occurrence of intracellular α-syn inclusions were quantified in four non-neuronal cell types-microglia, pericytes, astrocytes and oligodendrocytes as well as neurons in the anterior olfactory nucleus of post-mortem human pD olfactory bulbs (n = 11) and normal olfactory bulbs (n = 11). In the anterior olfactory nucleus, α-syn inclusions were confirmed to be intracellular in three of the four non-neuronal cell types, where 7.78% of microglia, 3.14% of pericytes and 1.97% of astrocytes were affected. Neurons containing α-syn inclusions comprised 8.60% of the total neuron population. oligodendrocytes did not contain α-syn. the data provides evidence that non-neuronal cells in the pD olfactory bulb contain α-syn inclusions, suggesting that they may play an important role in the progression of pD.
In Parkinson’s disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Zinc was high in these regions, and free zinc was detected in Lewy bodies, mitochondria, and lipofuscin of cells in the anterior olfactory nucleus. Increased iron and sodium in the human PD olfactory bulb may relate to the loss of olfactory function. In contrast, colocalization of free zinc and alpha-synuclein in the anterior olfactory nucleus implicate zinc in PD pathogenesis.
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