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  1. Article ; Online: Generation of Cholinergic and Dopaminergic Interneurons from Human Pluripotent Stem Cells as a Relevant Tool for In Vitro Modeling of Neurological Disorders Pathology and Therapy

    Anna Ochalek / Karolina Szczesna / Paolo Petazzi / Julianna Kobolak / Andras Dinnyes

    Stem Cells International, Vol

    2016  Volume 2016

    Abstract: The cellular and molecular bases of neurological diseases have been studied for decades; however, the underlying mechanisms are not yet fully elucidated. Compared with other disorders, diseases of the nervous system have been very difficult to study ... ...

    Abstract The cellular and molecular bases of neurological diseases have been studied for decades; however, the underlying mechanisms are not yet fully elucidated. Compared with other disorders, diseases of the nervous system have been very difficult to study mainly due to the inaccessibility of the human brain and live neurons in vivo or in vitro and difficulties in examination of human postmortem brain tissue. Despite the availability of various genetically engineered animal models, these systems are still not adequate enough due to species variation and differences in genetic background. Human induced pluripotent stem cells (hiPSCs) reprogrammed from patient somatic cells possess the potential to differentiate into any cell type, including neural progenitor cells and postmitotic neurons; thus, they open a new area to in vitro modeling of neurological diseases and their potential treatment. Currently, many protocols for generation of various neuronal subtypes are being developed; however, most of them still require further optimization. Here, we highlight accomplishments made in the generation of dopaminergic and cholinergic neurons, the two subtypes most affected in Alzheimer’s and Parkinson’s diseases and indirectly affected in Huntington’s disease. Furthermore, we discuss the potential role of hiPSC-derived neurons in the modeling and treatment of neurological diseases related to dopaminergic and cholinergic system dysfunction.
    Keywords Internal medicine ; RC31-1245
    Subject code 571
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Neurosphere Based Differentiation of Human iPSC Improves Astrocyte Differentiation

    Shuling Zhou / Karolina Szczesna / Anna Ochalek / Julianna Kobolák / Eszter Varga / Csilla Nemes / Abinaya Chandrasekaran / Mikkel Rasmussen / Susanna Cirera / Poul Hyttel / András Dinnyés / Kristine K. Freude / Hasan X. Avci

    Stem Cells International, Vol

    2016  Volume 2016

    Abstract: Neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) are traditionally maintained and proliferated utilizing two-dimensional (2D) adherent monolayer culture systems. However, NPCs cultured using this system hardly ... ...

    Abstract Neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) are traditionally maintained and proliferated utilizing two-dimensional (2D) adherent monolayer culture systems. However, NPCs cultured using this system hardly reflect the intrinsic spatial development of brain tissue. In this study, we determined that culturing iPSC-derived NPCs as three-dimensional (3D) floating neurospheres resulted in increased expression of the neural progenitor cell (NPC) markers, PAX6 and NESTIN. Expansion of NPCs in 3D culture methods also resulted in a more homogenous PAX6 expression when compared to 2D culture methods. Furthermore, the 3D propagation method for NPCs resulted in a significant higher expression of the astrocyte markers GFAP and aquaporin 4 (AQP4) in the differentiated cells. Thus, our 3D propagation method could constitute a useful tool to promote NPC homogeneity and also to increase the differentiation potential of iPSC towards astrocytes.
    Keywords Internal medicine ; RC31-1245
    Subject code 571
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Circadian cycle-dependent MeCP2 and brain chromatin changes.

    Alexia Martínez de Paz / Jose Vicente Sanchez-Mut / Mireia Samitier-Martí / Paolo Petazzi / Mauricio Sáez / Karolina Szczesna / Dori Huertas / Manel Esteller / Juan Ausió

    PLoS ONE, Vol 10, Iss 4, p e

    2015  Volume 0123693

    Abstract: Methyl CpG binding protein 2 (MeCP2) is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian ... ...

    Abstract Methyl CpG binding protein 2 (MeCP2) is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice

    Olga C. Jorge-Torres / Karolina Szczesna / Laura Roa / Carme Casal / Louisa Gonzalez-Somermeyer / Marta Soler / Cecilia D. Velasco / Pablo Martínez-San Segundo / Paolo Petazzi / Mauricio A. Sáez / Raúl Delgado-Morales / Stephane Fourcade / Aurora Pujol / Dori Huertas / Artur Llobet / Sonia Guil / Manel Esteller

    Cell Reports, Vol 23, Iss 6, Pp 1665-

    2018  Volume 1677

    Abstract: Summary: Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here ...

    Abstract Summary: Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763. : Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by loss-of-function mutations in the MeCP2 gene. Jorge-Torres et al. show that mice models of RTT display hyperactivation of Gsk3b kinase and neuroinflammation. Inhibition of the Gsk3b pathway partially rescues the phenotype and affects neuronal morphology and synaptic activity. Keywords: Rett syndrome, Gsk3b, Nfkb1, neurons, mice models, SB216763, neuroinflammation, Mecp2
    Keywords Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction

    Paula Lopez-Serra / Miguel Marcilla / Alberto Villanueva / Antonio Ramos-Fernandez / Anna Palau / Lucía Leal / Jessica E. Wahi / Fernando Setien-Baranda / Karolina Szczesna / Catia Moutinho / Anna Martinez-Cardus / Holger Heyn / Juan Sandoval / Sara Puertas / August Vidal / Xavier Sanjuan / Eva Martinez-Balibrea / Francesc Viñals / Jose C. Perales /
    Jesper B. Bramsem / Torben F. Ørntoft / Claus L. Andersen / Josep Tabernero / Ultan McDermott / Matthew B. Boxer / Matthew G. Vander Heiden / Juan Pablo Albar / Manel Esteller

    Nature Communications, Vol 7, Iss 1, Pp 1-

    Corrigendum: A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

    2016  Volume 2

    Abstract: Nature Communications 5: Article number: 4608 (2014); Published: 3 April 2014; Updated: 2 November 2016 During the preparation of the PCR gel panels in Fig. 1b,c, duplicate or otherwise irrelevant lanes were excised; these excisions were not noted in the ...

    Abstract Nature Communications 5: Article number: 4608 (2014); Published: 3 April 2014; Updated: 2 November 2016 During the preparation of the PCR gel panels in Fig. 1b,c, duplicate or otherwise irrelevant lanes were excised; these excisions were not noted in the published figure as per the Nature journal policy.
    Keywords Science ; Q
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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