Myelinosome Organelles in the Retina of R6/1 Huntington Disease (HD) Mice: Ubiquitous Distribution and Possible Role in Disease Spreading

Visual deficit is one of the complications of Huntington disease (HD), a fatal neurological disorder caused by CAG trinucleotide expansions in the Huntingtin gene, leading to the production of mutant Huntingtin (mHTT) protein. Transgenic HD R6/1 mice expressing human HTT exon1 with 115 CAG repeats recapitulate major features of the human pathology and exhibit a degeneration of the retina. Our aim was to gain insight into the ultrastructure of the pathological HD R6/1 retina by electron microscopy (EM). We show that the HD R6/1 retina is enriched with unusual organelles myelinosomes, produced by retinal neurons and glia. Myelinosomes are present in all nuclear and plexiform layers, in the synaptic terminals of photoreceptors, in the processes of retinal neurons and glial cells, and in the subretinal space. In vitro study shows that myelinosomes secreted by human retinal glial Müller MIO-M1 cells transfected with EGFP-mHTT-exon1 carry EGFP-mHTT-exon1 protein, as revealed by immuno-EM and Western-blotting. Myelinosomes loaded with mHTT-exon1 are incorporated by naive neuronal/neuroblastoma SH-SY5Y cells. This results in the emergence of mHTT-exon1 in recipient cells. This process is blocked by membrane fusion inhibitor MDL 28170. Conclusion: Incorporation of myelinosomes carrying mHTT-exon1 in recipient cells may contribute to HD spreading in the retina. Exploring ocular fluids for myelinosome presence could bring an additional biomarker for HD diagnostics.

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IN VITRO STUDY OF BONE MARROW

Blood ◽

10.1182/blood.v2.special_issue_number_1.33.33 ◽

1947 ◽

Vol 2 (Special_Issue_Number_1) ◽

pp. 33-41 ◽

Cited By ~ 7

Author(s):

CLAUS MUNK PLUM

Keyword(s):

Bone Marrow ◽

In Vitro Study ◽

Vitro Study ◽

Insight Into

Abstract Two types of apparatus are described for the culture of bone marrow in vitro. The first, a macro method, is suited to the study of large amounts of bone marrow. The second, a micro method, allows observations of the development of individual cells. Studies of erythropoiesis by these technics has allowed insight into production of erythrocytes. These data will be reported in a subsequent article.

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A Two-Step Immunomagnetic Microbead-Based Method for the Isolation of Human Primary Skin Telocytes/CD34+ Stromal Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21165877 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5877 ◽

Cited By ~ 2

Author(s):

Eloisa Romano ◽

Irene Rosa ◽

Bianca Saveria Fioretto ◽

Elena Lucattelli ◽

Marco Innocenti ◽

...

Keyword(s):

Stromal Cells ◽

Functional Data ◽

Cell Separation ◽

Negative Selection ◽

Immune Surveillance ◽

In Vitro Study ◽

Homeostasis Regulation ◽

Selection For ◽

Insight Into

Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority of studies investigating these cells are mainly descriptive and focus only on their morphology, with a consequent paucity of functional data. To gain relevant insight into the possible functions of TCs, in vitro analyses are clearly required, but currently, the protocols for TC isolation are only at the early stages and not fully standardized. In the present in vitro study, we describe a novel methodology for the purification of human primary skin TCs through a two-step immunomagnetic microbead-based cell separation (i.e., negative selection for CD31 followed by positive selection for CD34) capable of discriminating these cells from other connective tissue-resident cells on the basis of their different immunophenotypic features. Our experiments clearly demonstrated that the proposed method allows a selective purification of cells exhibiting the peculiar TC morphology. Isolated TCs displayed very long cytoplasmic extensions with a moniliform silhouette (telopodes) and presented an immunophenotypic profile (CD31−/CD34+/PDGFRα+/vimentin+) that unequivocally differentiates them from endothelial cells (CD31+/CD34+/PDGFRα−/vimentin+) and fibroblasts (CD31−/CD34−/PDGFRα+/vimentin+). This novel methodology for the isolation of TCs lays the groundwork for further research aimed at elucidating their functional properties and possible translational applications, especially in the field of regenerative medicine.

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Insight into the collagen assembly in the presence of lysine and glutamic acid: An in vitro study

Materials Science and Engineering C ◽

10.1016/j.msec.2016.09.037 ◽

2017 ◽

Vol 70 ◽

pp. 689-700 ◽

Cited By ~ 19

Author(s):

Xinhua Liu ◽

Nianhua Dan ◽

Weihua Dan

Keyword(s):

Glutamic Acid ◽

In Vitro Study ◽

Vitro Study ◽

Insight Into

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Modulation of CaCO3 Phase and Morphology by Tuning the Sequence of Addition: An Insight into the Formation of Monohydrocalcite

New Journal of Chemistry ◽

10.1039/d1nj03707b ◽

2021 ◽

Author(s):

Debojit Paul ◽

Deepa Sachan ◽

Subhadeep De ◽

Gopal Das

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Insight Into

The ability of the organisms to tune among the various phases of biominerals with exquisitely beautiful morphologies is very appealing. This study aims to perform an in vitro study of...

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A Simulator for the In Vitro Study of the Dynamics of the Aortic Valve: Design and Test

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206121 ◽

2009 ◽

Author(s):

Riccardo Vismara ◽

Dario Comparolo ◽

Andrea Mangini ◽

Carlo Antona ◽

Gianfranco B. Fiore

Keyword(s):

Animal Models ◽

Aortic Valve ◽

Heart Valves ◽

In Vitro Study ◽

Vitro Study ◽

Valve Design ◽

Experimental Conditions ◽

Insight Into ◽

Physiological Complexity

The in vitro approach to the study of the hemodynamics of heart valves allows easier-to-control and well repeatable experimental conditions, if compared with studies on animal models. A deep, detailed insight into specific issues is possible, despite the unavoidable simplification of the physiological complexity.

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Human Mesenchymal Stem Cells Expressing Erythropoietin Enhance Survivability of Retinal Neurons Against Oxidative Stress: An In Vitro Study

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2018.00190 ◽

2018 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Suet Lee Shirley Ding ◽

Suresh Kumar ◽

Mohammed Safwan Ali Khan ◽

Pooi Ling Mok

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

In Vitro Study ◽

Vitro Study ◽

Retinal Neurons

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Pro-apoptotic effects of micro-ribonucleic acid-365 on retinal neurons by targeting insulin-like growth factor-1 in diabetic rats: An in vivo and in vitro study

Journal of Diabetes Investigation ◽

10.1111/jdi.12815 ◽

2018 ◽

Vol 9 (5) ◽

pp. 1041-1051 ◽

Cited By ~ 4

Author(s):

Kairong Zheng ◽

Ning Wang ◽

Yinchen Shen ◽

Zhihua Zhang ◽

Qing Gu ◽

...

Keyword(s):

Growth Factor ◽

Ribonucleic Acid ◽

In Vitro Study ◽

Diabetic Rats ◽

Vitro Study ◽

Insulin Like Growth Factor ◽

Retinal Neurons ◽

Apoptotic Effects

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The Antiglycoxidative Ability of Selected Phenolic Compounds—An In Vitro Study

Molecules ◽

10.3390/molecules24152689 ◽

2019 ◽

Vol 24 (15) ◽

pp. 2689 ◽

Cited By ~ 1

Author(s):

Agnieszka Piwowar ◽

Anna Rorbach-Dolata ◽

Izabela Fecka

Keyword(s):

Phenolic Compounds ◽

In Vitro Study ◽

Vitro Study ◽

Physiological Properties ◽

Glycation End Products ◽

Pharmacological Studies ◽

Ferulic Acids ◽

And Oxidative Stress ◽

Insight Into

Hyperglycemia and oxidative stress may be observed in different diseases as important factors connected with their development. They often occur simultaneously and are considered together as one process: Glycoxidation. This can influence the function or structure of many macromolecules, for example albumin, by changing their physiological properties. This disturbs the homeostasis of the organism, so the search for natural compounds able to inhibit the glycoxidation process is a current and important issue. The aim of this study was the examination of the antiglycoxidative capacity of 16 selected phenolic compounds, belonging to three phenolic groups, as potential therapeutic agents. Their antiglycoxidative ability, in two concentrations (2 and 20 µM), were examined by in vitro study. The inhibition of the formation of both glycoxidative products (advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)) were assayed. Stronger antiglycoxidative action toward the formation of both AOPPs and AGEs was observed for homoprotocatechuic and ferulic acids in lower concentrations, as well as catechin, quercetin, and 8-O-methylurolithin A in higher concentrations. Homoprotocatechuic acid demonstrated the highest antiglycoxidative capacity in both examined concentrations and amongst all of them. A strong, significant correlation between the percentage of AOPPs and AGEs inhibition by compounds from all phenolic groups, in both examined concentrations, was observed. The obtained results give an insight into the antiglycoxidative potential of phenolic compounds and indicate homoprotocatechuic acid to be the most promising antiglycoxidative agent, but further biological and pharmacological studies are needed.

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Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1807962115 ◽

2018 ◽

Vol 115 (37) ◽

pp. E8765-E8774 ◽

Cited By ~ 22

Author(s):

Florian A. Siebzehnrübl ◽

Kerstin A. Raber ◽

Yvonne K. Urbach ◽

Anja Schulze-Krebs ◽

Fabio Canneva ◽

...

Keyword(s):

Neuronal Differentiation ◽

Huntington Disease ◽

Neurodegenerative Disorder ◽

Cag Repeats ◽

Interventional Treatment ◽

Prodromal Phase ◽

Increased Risk ◽

Dopaminergic Regulation

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD.

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