EURON and THEME joint PhD meeting

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Investigating the role of microRNAs in Spinocerebellar Ataxia type 3 Rohit Nalavade 74 EURON and THEME joint meeting 2011 DZNE, German Center for Neurodegenerative Disases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany Spinocerebellar Ataxia type 3 (SCA3) is an autosomal, dominantly inherited disorder belonging to the group of polyglutamine repeat (polyQ) diseases. It is caused by CAG repeat expansions in the SCA3 gene coding for polyglutamine repeat expansions in the Ataxin-3 (At3) protein. The disease is characterized by intranuclear aggregates and progressive neuronal cell death especially in the cerebellum and the brain stem. MicroRNAs (miRNAs) have been shown to play important roles in neurodegenerative diseases. This study aims to investigate if miRNAs play a role in regulation of At3 protein expression. MiRNA profiling and target prediction software have suggested the involvement of miRNAs in regulation of At3 expression. Further experiments using constructs including 3’ Un-Translated Region (UTR) of At3 mRNA coupled with luciferase and lentiviral constructs for over-expression of these miRNAs have backed the initial results suggesting that some of these miRNAs may indeed play a role. A promising recent development has been the use of neurons derived from IPSCs (Induced Pleuripotent Stem Cells) from patients of SCA3 as a system to study various aspects of the disease. Assessment of the miRNA profile of these neurons and their further use in experiments involving modulations of specific miRNA levels is expected to provide vital insights regarding the role of miRNAs in SCA3.
75 EURON and THEME joint meeting 2011 Development of an in vitro system for the assessment of axon growth promoting properties of bioengineered scaffolds Gerardo-Nava J 1,2 , Grehl T 3 , Weis J 2 , Steinbusch HWM 1 , Brook GA 2 . 1 Maastricht University, School of Mental Health and Neurosciences; 2 RWTH Aachen University Hospital, Institute of Neuropathology; 3 Ruhr-University-Bochum, Department of Neurology. An in vitro model capable of studying the axon growth promoting properties of 3D biomaterials will be useful in the development of scaffolds for the repair of traumatically injured peripheral nervous system (PNS) tissues. The well preserved cytoarchitectural organization of spinal cord organotypic slice cultures (SCOSC) as well as hemisected dorsal root ganglia (DRG) are being used to determine the orientated motor- and sensory axon growth promoting properties of a 3D collagen scaffold. Sensory neurons from hemisected DRGs extended long and highly orientated SMI32-positive axons throughout the Matricel collagen microchannels as well as along the surface of the scaffold. Axons that reached the dorsal horn of the SCOSC crossed the scaffold-SCOSC interface and matrix crossing it and exploring the target tissue of the DH of the organotypic slice cultures. Similarly, ventral horn motor neuron axons (also SMI-32 positive) from the of slice cultures extend within and along the surface of the scaffold. In both cases, a close interaction between regenerating axonal profiles and NGFr/p75postive Schwann cells could be seen. Cell migration into the collagen scaffold was strong in both experimental set-ups and included migration by cells that were immunoreactive for NGFr/p75, S100, IBA1 and ED1. A more limited degree of GFAP-positive astrocyte migration was observed close to the SCOSC-scaffold interface. Earlier in vitro investigations have focused largely on cell-substrate interactions using cell suspensions and 2D biomaterials. As the field of biomaterial research advances in the development of 3D scaffolds, the utilization of in vitro models capable of analyzing the tissue-scaffold interactions may generate much useful information. In particular, it is hoped that such approaches will eventually reduce the number of animals required in the development of bioengineering strategies intended for PNS repair.
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EURON and THEME joint PhD meeting U
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The local organizing committee: Pro
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Information about THEME 3 EURON and
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5 EURON and THEME joint meeting 201
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EURON a short introduction 7 EURON
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Programme 13 EURON and THEME joint
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Thursday September 22 nd 9:00 - 10:
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Friday September 23 rd 17 EURON and
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Poster presentations 19 EURON and T
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Page 25 and 26: EURON Lecture Frank Kirchhoff ADDRE
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Page 29 and 30: THEME Lecture Eckhard Mandelkow POS
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Page 105 and 106: List of Participants 103 EURON and
Page 107 and 108: Nuersailike Abuduwali University of
Page 109 and 110: Marianne Eisenhardt University of B
Page 111 and 112: Sabine Klein University of Bonn PhD
Page 113 and 114: Viktoriya Peeva University of Bonn
Page 115: Sylvie van der Kruijs Maastricht Un
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EURON and THEME joint PhD meeting

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