scholarly journals Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy

2018 ◽  
Vol 19 (12) ◽  
pp. 4129 ◽  
Author(s):  
Dario Valdinocci ◽  
Rowan Radford ◽  
Michael Goulding ◽  
Junna Hayashi ◽  
Roger Chung ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Disease Process ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Cell Types ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Extracellular Milieu ◽  
The Brain

Multiple system atrophy, characterized by atypical Parkinsonism, results from central nervous system (CNS) cell loss and dysfunction linked to aggregates of the normally pre-synaptic α-synuclein protein. Mostly cytoplasmic pathological α-synuclein inclusion bodies occur predominantly in oligodendrocytes in affected brain regions and there is evidence that α-synuclein released by neurons is taken up preferentially by oligodendrocytes. However, extracellular α-synuclein has also been shown to interact with other neural cell types, including astrocytes and microglia, as well as extracellular factors, mediating neuroinflammation, cell-to-cell spread and other aspects of pathogenesis. Here, we review the current evidence for how α-synuclein present in the extracellular milieu may act at the cell surface to drive components of disease progression. A more detailed understanding of the important extracellular interactions of α-synuclein with neuronal and non-neuronal cell types both in the brain and periphery may provide new therapeutic targets to modulate the disease process.

scholarly journals Potential Modes of Intercellular Alpha-Synuclein Transmission

2017 ◽  
Author(s):  
Dario Valdinocci ◽  
Rowan A. W. Radford ◽  
Sue Maye Siow ◽  
Roger S. Chung ◽  
Dean L. Pountney
Keyword(s):  
Lewy Bodies ◽  
Cell Loss ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Disease Propagation ◽  
Major Mode ◽  
Mediate Cytotoxicity ◽  
Progression Of Disease ◽  
Intracellular Aggregates

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

2021 ◽  
Author(s):  
Shachar Sherman ◽  
Koichi Kawakami ◽  
Herwig Baier
Keyword(s):  
Visual Information ◽  
Visual Stimulation ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Vertebrate Brain ◽  
Relative Contribution ◽  
Retinal Input ◽  
And Migration ◽  
The Brain

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.

scholarly journals Neuronal apoptosis: signal and cell diversity

1969 ◽  
Vol 40 (1) ◽  
pp. 124-133
Author(s):  
Lina Vanessa Becerra ◽  
Hernán José Pimienta
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neuronal Response ◽  
Neuronal Cell ◽  
Cell Types ◽  
Point Of View ◽  
Trophic Factors ◽  
Cell Diversity ◽  
Apoptotic Pathways ◽  
The Brain

Programmed cell death occurs as a physiological process during development. In the brain and spinal cord this event determines the number and location of the different cell types. In adulthood, programmed cell death or apoptosis is more restricted but it may play a major role in different acute and chronic pathological entities. However, in contrast to other tissues where apoptosis has been widely documented from a morphological point of view, in the central nervous system complete anatomical evidence of apoptosis is scanty. In spite of this there is consensus about the activation of different signal systems associated to programmed cell death. In the present article we attempt to summarize the main apoptotic pathways so far identified in nervous tissue. Considering that apoptotic pathways are multiple, the neuronal cell types are highly diverse and specialized and that neuronal response to injury and survival depends upon tissue context, (i.e., preservation of connectivity, glial integrity and cell matrix, blood supply and trophic factors availability) what is relevant for the apoptotic process in a sector of the brain may not be important in another.

scholarly journals Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit

2021 ◽  
Vol 15 ◽  
Author(s):  
Louis-Philippe Bernier ◽  
Clément Brunner ◽  
Azzurra Cottarelli ◽  
Matilde Balbi
Keyword(s):  
Brain Function ◽  
Energy Demand ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Brain Regions ◽  
Regional Heterogeneity ◽  
Regional Specialization ◽  
Multiple Cell ◽  
Cellular Components ◽  
The Brain

The neurovascular unit (NVU) of the brain is composed of multiple cell types that act synergistically to modify blood flow to locally match the energy demand of neural activity, as well as to maintain the integrity of the blood-brain barrier (BBB). It is becoming increasingly recognized that the functional specialization, as well as the cellular composition of the NVU varies spatially. This heterogeneity is encountered as variations in vascular and perivascular cells along the arteriole-capillary-venule axis, as well as through differences in NVU composition throughout anatomical regions of the brain. Given the wide variations in metabolic demands between brain regions, especially those of gray vs. white matter, the spatial heterogeneity of the NVU is critical to brain function. Here we review recent evidence demonstrating regional specialization of the NVU between brain regions, by focusing on the heterogeneity of its individual cellular components and briefly discussing novel approaches to investigate NVU diversity.

scholarly journals 6B4 proteoglycan/phosphacan is a repulsive substratum but promotes morphological differentiation of cortical neurons

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 647-658
Author(s):  
N. Maeda ◽  
M. Noda
Keyword(s):  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Tyrosine Phosphatase ◽  
Neuronal Cell ◽  
Morphological Differentiation ◽  
Cell Types ◽  
Thalamic Neurons ◽  
Neurite Extension ◽  
The Brain

6B4 proteoglycan/phosphacan is one of the major phosphate-buffered saline-soluble chondroitin sulfate proteoglycans of the brain. Recently, this molecule has been demonstrated to be an extracellular variant of the proteoglycan-type protein tyrosine phosphatase, PTPzeta (RPTPbeta). The influence of the 6B4 proteoglycan, adsorbed onto the substratum, on cell adhesion and neurite outgrowth was studied using dissociated neurons from the cerebral cortex and thalamus. 6B4 proteoglycan adsorbed onto plastic tissue culture dishes did not support neuronal cell adhesion, but rather exerted repulsive effects on cortical and thalamic neurons. When neurons were densely seeded on patterned substrata consisting of a grid-like structure of alternating poly-L-lysine and 6B4 proteoglycan-coated poly-L-lysine domains, they were concentrated on the poly-L-lysine domains. However, 6B4 proteoglycan did not retard the differentiation of neurons but rather promoted neurite outgrowth and development of the dendrites of cortical neurons, when neurons were sparsely seeded on poly-L-lysine-conditioned coverslips continuously coated with 6B4 proteoglycan. This effect of 6B4 proteoglycan on the neurite extension of cortical neurons was apparent even on coverslips co-coated with fibronectin or tenascin. By contrast, the neurite extension of thalamic neurons was not modified by 6B4 proteoglycan. Chondroitinase ABC or keratanase digestion of 6B4 proteoglycan did not affect its neurite outgrowth promoting activity, but a polyclonal antibody against 6B4 proteoglycan completely suppressed this activity, suggesting that a protein moiety is responsible for the activity. 6B4 proteoglycan transiently promoted tyrosine phosphorylation of an 85x10(3) Mr protein in the cortical neurons, which correlated with the induction of neurite outgrowth. These results suggest that 6B4 proteoglycan/phosphacan modulates morphogenesis and differentiation of neurons dependent on its spatiotemporal distribution and the cell types in the brain.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

scholarly journals Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

2016 ◽  
Vol 113 (21) ◽  
pp. 6029-6034 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica A. Carrasco ◽  
Peri T. Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

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