المؤلفون: Matthew D Snape, Melanie Gündert, Anette-Gabriele Ziegler, Peter Achenbach, Reinhard Berner, Kristina Casteels, Thomas Danne, Joerg Hasford, Olga Kordonouri, Karin Lange, Helena Elding Larsson, Markus Lundgren, Agnieszka Szypowska, John A Todd, Ezio Bonifacio, Nicole Zubizarreta, Christiane Winkler, Åke Lernmark, Daniel Agardh, Cigdem Gezginci, Claudia Ramminger, Marlon Scholz, Katharina Warncke, Carin Andrén Aronsson, Rasmus Bennet, Lina Fransson, Zeliha Mestan, Caroline Nilsson, Anita Ramelius, Carina Törn, Sarah Hogg, Catherine Owen, Lidia Groele, Florian Haupt, Claudia Matzke, Robin Assfalg, Matthew Snape, Felix Reschke, Marcin L Pekalski, Andreas Weiss, Andrew Johnston, Manja Jolink, Loredana Marcovecchio, Mariusz Ołtarzewski, Stefanie Arnolds, Annika Kölln, Markus Pfirrmann, Corinna Barz, Karina Blasius, Nadine Friedl, Adriano Gomez-Bantel, Martin Heigermoser, Bianca Höfelschweiger, Nadine Klein, Ramona Lickert, Rebecca Niewöhner, Katharina Schütte-Borkovec, Mira Taulien, Lara Vogel, Franziska Voß, José Maria Zapardiel Gonzalo, Philipp Sifft, Heidi Kapfelsberger, Merve Vurucu, Katharina Sarcletti, Stefanie Jacobson, Yulia Grinin, John A. Todd, Anette-G. Ziegler, Marcin L. Pekalski, Anette G. Ziegler, Annre Rochtus, An Jacobs, Jasmin Paulus, Brontë Vrancken, Natalie Van den Driessche, Renka Van Heyste, Janne Houben, Veerle Vanhuyse, Sevina Dietz, Gita Gemulla, Manja Gottschalk-Schwarz, Sophie Heinke, Angela Hommel, Susann Kowal, Fabian Lander, Robert Morgenstern, Marc Weigelt, Sari Arabi, Raphael Hoffmann, Ruth Blechschmidt, Franziska Ehrlich, Anja Loff, Laura Galuschka, Ute Holtkamp, Nils Janzen, Sarah Landsberg, Erika Marquardt, Frank Roloff, Kerstin Semler, Thekla von dem Berge, Melanie Bunk, Simone Färber-Meisterjahn, Willi Grätz, Ines Greif, Melanie Herbst, Anna Hofelich, Benjamin Marcus, Annette Munzinger, Jasmin Ohli, Franziska Reinmüller, Tiziana Welzhofer, Sylwia Dybkowska, Katarzyna Dżygało, Dorota Owczarek, Katarzyna Popko, Agnieszka Skrobot, Anna Taczanowska, Beata Zduńczyk, Charlotte Brundin, Ida Jönsson, Sara Maroufkhani, Evelyn Tekum Amboh, Katarzyna Gajewska-Knapik, Elena Romero, Suzannah Twiss, Helen Gallon, Laura Gebbie, Fiona Jenkinson, Steven Pratt, Steve Robson, Claire Simmister, Evelyn Thomson, Eileen Walton

المصدر: BMJ Open, Vol 11, Iss 11 (2021)

مصطلحات موضوعية: Medicine

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/11/11/e052449.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/32b6df3b92764c4e9ef877d2ae7501a4Test

المؤلفون: Frank Roloff, Hannah Scheiblich, Carola Dewitz, Silke Dempewolf, Michael Stern, Gerd Bicker

المصدر: PLoS ONE, Vol 10, Iss 2, p e0118536 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4340918?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/a2030bebe1b94331b6d26e2e3557806fTest

المؤلفون: Frank Roloff, Sarah Strauß, Peter M. Vogt, Gerd Bicker, Christine Radtke

المصدر: BioMed Research International, Vol 2014 (2014)

مصطلحات موضوعية: Medicine

الوصف: Over the last years, a number of therapeutic strategies have emerged to promote axonal regeneration. An attractive strategy is the implantation of biodegradable and nonimmunogenic artificial scaffolds into injured peripheral nerves. In previous studies, transplantation of decellularized veins filled with spider silk for bridging critical size nerve defects resulted in axonal regeneration and remyelination by invading endogenous Schwann cells. Detailed interaction of elongating neurons and the spider silk as guidance material is unknown. To visualize direct cellular interactions between spider silk and neurons in vitro, we developed an in vitro crossed silk fiber array. Here, we describe in detail for the first time that human (NT2) model neurons attach to silk scaffolds. Extending neurites can bridge gaps between single silk fibers and elongate afterwards on the neighboring fiber. Culturing human neurons on the silk arrays led to an increasing migration and adhesion of neuronal cell bodies to the spider silk fibers. Within three to four weeks, clustered somata and extending neurites formed ganglion-like cell structures. Microscopic imaging of human neurons on the crossed fiber arrays in vitro will allow for a more efficient development of methods to maximize cell adhesion and neurite growth on spider silk prior to transplantation studies.

العلاقة: http://dx.doi.org/10.1155/2014/906819Test; https://doaj.org/toc/2314-6133Test; https://doaj.org/toc/2314-6141Test; https://doaj.org/article/c3cc5af39b1d4956ba198eb77c170cacTest

الإتاحة: https://doi.org/10.1155/2014/906819Test
https://doaj.org/article/c3cc5af39b1d4956ba198eb77c170cacTest

المؤلفون: Matthew D Snape, Melanie Gündert, Anette-Gabriele Ziegler, Peter Achenbach, Reinhard Berner, Kristina Casteels, Thomas Danne, Joerg Hasford, Olga Kordonouri, Karin Lange, Helena Elding Larsson, Markus Lundgren, Agnieszka Szypowska, John A Todd, Ezio Bonifacio, Nicole Zubizarreta, Christiane Winkler, Åke Lernmark, Daniel Agardh, Cigdem Gezginci, Claudia Ramminger, Marlon Scholz, Katharina Warncke, Carin Andrén Aronsson, Rasmus Bennet, Lina Fransson, Zeliha Mestan, Caroline Nilsson, Anita Ramelius, Carina Törn, Sarah Hogg, Catherine Owen, Lidia Groele, Florian Haupt, Claudia Matzke, Robin Assfalg, Matthew Snape, Felix Reschke, Marcin L Pekalski, Andreas Weiss, Andrew Johnston, Manja Jolink, Loredana Marcovecchio, Mariusz Ołtarzewski, Stefanie Arnolds, Annika Kölln, Markus Pfirrmann, Corinna Barz, Karina Blasius, Nadine Friedl, Adriano Gomez-Bantel, Martin Heigermoser, Bianca Höfelschweiger, Nadine Klein, Ramona Lickert, Rebecca Niewöhner, Katharina Schütte-Borkovec, Mira Taulien, Lara Vogel, Franziska Voß, José Maria Zapardiel Gonzalo, Philipp Sifft, Heidi Kapfelsberger, Merve Vurucu, Katharina Sarcletti, Stefanie Jacobson, Yulia Grinin, John A. Todd, Anette-G. Ziegler, Marcin L. Pekalski, Anette G. Ziegler, Annre Rochtus, An Jacobs, Jasmin Paulus, Brontë Vrancken, Natalie Van den Driessche, Renka Van Heyste, Janne Houben, Veerle Vanhuyse, Sevina Dietz, Gita Gemulla, Manja Gottschalk-Schwarz, Sophie Heinke, Angela Hommel, Susann Kowal, Fabian Lander, Robert Morgenstern, Marc Weigelt, Sari Arabi, Raphael Hoffmann, Ruth Blechschmidt, Franziska Ehrlich, Anja Loff, Laura Galuschka, Ute Holtkamp, Nils Janzen, Sarah Landsberg, Erika Marquardt, Frank Roloff, Kerstin Semler, Thekla von dem Berge, Melanie Bunk, Simone Färber-Meisterjahn, Willi Grätz, Ines Greif, Melanie Herbst, Anna Hofelich, Benjamin Marcus, Annette Munzinger, Jasmin Ohli, Franziska Reinmüller, Tiziana Welzhofer, Sylwia Dybkowska, Katarzyna Dżygało, Dorota Owczarek, Katarzyna Popko, Agnieszka Skrobot, Anna Taczanowska, Beata Zduńczyk, Charlotte Brundin, Ida Jönsson, Sara Maroufkhani, Evelyn Tekum Amboh, Katarzyna Gajewska-Knapik, Elena Romero, Suzannah Twiss, Helen Gallon, Laura Gebbie, Fiona Jenkinson, Steven Pratt, Steve Robson, Claire Simmister, Evelyn Thomson, Eileen Walton

المصدر: BMJ Open, Vol 11, Iss 11 (2021)
BMJ Open
BMJ Open 11:e052449 (2021)

مصطلحات موضوعية: Diabetes & Endocrinology, Epidemiology, General Diabetes, Immunology, Paediatrics, CHILDHOOD, diabetes & endocrinology, CHILDREN, PROGRESSION, Autoimmunity, GUT MICROBIOME, Coeliac disease, law.invention, immunology, Randomized controlled trial, law, Multicenter Studies as Topic, Cumulative incidence, Family history, Child, Randomized Controlled Trials as Topic, RISK, Respiratory infection, General Medicine, ddc, Diabetes and Endocrinology, Medicine, epidemiology, Life Sciences & Biomedicine, medicine.medical_specialty, Bifidobacterium longum subspecies infantis, paediatrics, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Type 1 diabetes, Science & Technology, business.industry, general diabetes, Autoantibody, Infant, medicine.disease, Gastrointestinal Microbiome, Diabetes Mellitus, Type 1, Dietary Supplements, BETA-CELL AUTOIMMUNITY, AUTOANTIBODIES, business

الوصف: IntroductionThe Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.Methods and analysisInfants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin.Ethics and disseminationThe study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study.Trial registration numberNCT04769037.

وصف الملف: application/pdf; Electronic

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::307df38401cb50d305c4eda84bd4c727Test
https://mediatum.ub.tum.de/doc/1653368/document.pdfTest

المؤلفون: Ariane Rode, Christina Zellinger, Sarah Fischborn, Natalie Seeger, Gerd Bicker, Hannes Wendt, Heidrun Potschka, Frank Roloff, Vera Russmann

المصدر: Epilepsia. 52:2333-2343

مصطلحات موضوعية: Neurogenesis, Central nervous system, Morris water navigation task, Status epilepticus, Pharmacology, Epileptogenesis, Neuroprotection, medicine.anatomical_structure, Neurology, Erythropoietin, medicine, Neurology (clinical), Analysis of variance, medicine.symptom, Psychology, Neuroscience, medicine.drug

الوصف: Summary Purpose: The selection of a minimal active sequence of erythropoietin allowed the design of peptide mimetics that exert beneficial effects in the central nervous system but lack an erythropoietic effect. Erythropoietin has been suggested as a promising therapeutic and prophylactic for epilepsies based on its neuroprotective, neuroregenerative, and antiinflammatory potency. Therefore, it is of particular interest to evaluate whether the nonerythropoietic erythropoietin-derived peptide pHBSP can affect epileptogenesis. Methods: In a post–status epilepticus model in rats, we determined the effects of pHBSP and of recombinant human erythropoietin with short-term administration following status epilepticus. Key Findings: Both pHBSP and erythropoietin further enhanced the status epilepticus–associated increase in hippocampal cell proliferation. Thereby, pHBSP seemed to promote neuronal differentiation and survival resulting in a significant increase in neurogenesis. Neither pHBSP nor erythropoietin affected the number of animals exhibiting spontaneous recurrent seizures as well as the seizure frequency in the chronic phase. In the Morris water maze, pHBSP attenuated cognitive deficits in epileptic animals. Significance: In conclusion, the helix B–derived erythropoietin peptide pHBSP can modulate the cellular and cognitive consequences of a status epilepticus. The impact of pHBSP on spatial learning might indicate that the peptide allows beneficial effects on epileptogenesis-associated cognitive deficits. However, it needs to be considered that learning deficits were not abolished by pHBSP and that the effects were not observed consistently until the end of the study. Therefore, adjustment of timing, duration, and dose of peptide administration might be necessary to further evaluate the efficacy of pHBSP.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4735317ad703ced1766e2cb835631e90Test
https://doi.org/10.1111/j.1528-1167.2011.03302.xTest

المؤلفون: Gerd Bicker, Peter M. Vogt, Sarah Strauß, Frank Roloff, Christine Radtke

المصدر: BioMed Research International
BioMed Research International, Vol 2014 (2014)

مصطلحات موضوعية: Article Subject, Neurite, Silk, lcsh:Medicine, macromolecular substances, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, medicine, Cell Adhesion, Animals, Humans, Spider silk, Remyelination, Cell adhesion, Decellularization, General Immunology and Microbiology, Tissue Scaffolds, lcsh:R, fungi, technology, industry, and agriculture, Biomaterial, Spiders, General Medicine, Anatomy, equipment and supplies, Axons, Cell biology, Nerve Regeneration, Transplantation, medicine.anatomical_structure, SILK, nervous system, Schwann Cells, Research Article

الوصف: Over the last years, a number of therapeutic strategies have emerged to promote axonal regeneration. An attractive strategy is the implantation of biodegradable and nonimmunogenic artificial scaffolds into injured peripheral nerves. In previous studies, transplantation of decellularized veins filled with spider silk for bridging critical size nerve defects resulted in axonal regeneration and remyelination by invading endogenous Schwann cells. Detailed interaction of elongating neurons and the spider silk as guidance material is unknown. To visualize direct cellular interactions between spider silk and neuronsin vitro, we developed anin vitrocrossed silk fiber array. Here, we describe in detail for the first time that human (NT2) model neurons attach to silk scaffolds. Extending neurites can bridge gaps between single silk fibers and elongate afterwards on the neighboring fiber. Culturing human neurons on the silk arrays led to an increasing migration and adhesion of neuronal cell bodies to the spider silk fibers. Within three to four weeks, clustered somata and extending neurites formed ganglion-like cell structures. Microscopic imaging of human neurons on the crossed fiber arraysin vitrowill allow for a more efficient development of methods to maximize cell adhesion and neurite growth on spider silk prior to transplantation studies.

وصف الملف: text/xhtml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffcc635a4f4d29eaff007ec46db4eb0aTest
http://europepmc.org/articles/PMC4052499Test

المؤلفون: Michael Stern, Vikramjeet Singh, Martin Stangel, Hannah Scheiblich, Gerd Bicker, Frank Roloff

المصدر: Brain research. 1564

مصطلحات موضوعية: Lipopolysaccharide, Motility, Inflammation, Biology, Nitric Oxide, Nitric oxide, Cell Line, Rats, Sprague-Dawley, chemistry.chemical_compound, Cell Movement, medicine, Animals, Cytoskeleton, Molecular Biology, Cyclic GMP, Microglia, General Neuroscience, Cell migration, Cell biology, Rats, medicine.anatomical_structure, chemistry, Neurology (clinical), medicine.symptom, Soluble guanylyl cyclase, Developmental Biology, Signal Transduction

الوصف: Microglia are the resident immune cells of the brain, which become rapidly activated and migrate to the site of insult in brain infection and disease. Activated microglia generate large amounts of the highly reactive messenger molecule nitric oxide (NO). NO is able to raise cyclic GMP levels via binding to soluble guanylyl cyclase. We investigated potential mechanistic links between inflammation, NO signaling, and microglial migration. To monitor cell migration, we used a scratch wound assay and compared results obtained in the BV-2 microglial line to primary microglia. Incubation with lipopolysaccharide (LPS) as stimulator of acute inflammatory processes enhanced migration of both microglial cell types. LPS activated NO production in BV-2 cells and application of an NO donor increased BV-2 cell migration while an NO scavenger reduced motility. Pharmacological inhibition of soluble guanylyl cyclase and the resulting decrease in motility can be rescued by a membrane permeant analog of cGMP. Despite differences in the threshold towards stimulation with the chemical agents, both BV-2 cells and primary microglia react in a similar way. The important role of NO/cGMP as positive regulator of microglial migration, the downstream targets of the signaling cascade, and resulting cytoskeletal changes can be conveniently investigated in a microglial cell line.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7427c0ec140d88c44637aa7a3548b6dTest
https://pubmed.ncbi.nlm.nih.gov/24713349Test

المؤلفون: Natalie, Seeger, Christina, Zellinger, Ariane, Rode, Frank, Roloff, Gerd, Bicker, Vera, Russmann, Sarah, Fischborn, Hannes, Wendt, Heidrun, Potschka

المصدر: Epilepsia. 52(12)

مصطلحات موضوعية: Analysis of Variance, Neurogenesis, Serine Endopeptidases, Adaptation, Physiological, Electric Stimulation, Rats, Rats, Sprague-Dawley, Disease Models, Animal, Status Epilepticus, Bromodeoxyuridine, Phosphopyruvate Hydratase, Exploratory Behavior, Animals, Humans, Female, Microglia, Cognition Disorders, Maze Learning, Erythropoietin, Cell Proliferation

الوصف: The selection of a minimal active sequence of erythropoietin allowed the design of peptide mimetics that exert beneficial effects in the central nervous system but lack an erythropoietic effect. Erythropoietin has been suggested as a promising therapeutic and prophylactic for epilepsies based on its neuroprotective, neuroregenerative, and antiinflammatory potency. Therefore, it is of particular interest to evaluate whether the nonerythropoietic erythropoietin-derived peptide pHBSP can affect epileptogenesis.In a post-status epilepticus model in rats, we determined the effects of pHBSP and of recombinant human erythropoietin with short-term administration following status epilepticus.Both pHBSP and erythropoietin further enhanced the status epilepticus-associated increase in hippocampal cell proliferation. Thereby, pHBSP seemed to promote neuronal differentiation and survival resulting in a significant increase in neurogenesis. Neither pHBSP nor erythropoietin affected the number of animals exhibiting spontaneous recurrent seizures as well as the seizure frequency in the chronic phase. In the Morris water maze, pHBSP attenuated cognitive deficits in epileptic animals.In conclusion, the helix B-derived erythropoietin peptide pHBSP can modulate the cellular and cognitive consequences of a status epilepticus. The impact of pHBSP on spatial learning might indicate that the peptide allows beneficial effects on epileptogenesis-associated cognitive deficits. However, it needs to be considered that learning deficits were not abolished by pHBSP and that the effects were not observed consistently until the end of the study. Therefore, adjustment of timing, duration, and dose of peptide administration might be necessary to further evaluate the efficacy of pHBSP.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::14d65f9329b731b4d2425807ae4df873Test
https://pubmed.ncbi.nlm.nih.gov/22050420Test

المؤلفون: Million Adane Tegenge, Gerd Bicker, Frank Roloff

المصدر: Cellular and molecular neurobiology. 31(4)

مصطلحات موضوعية: Forskolin, Embryonal Carcinoma Stem Cells, Neurite, Colforsin, Cell Differentiation, Cell Biology, General Medicine, Nestin, Biology, Cyclic AMP-Dependent Protein Kinases, Axons, Cell biology, Adenylyl cyclase, Cellular and Molecular Neuroscience, chemistry.chemical_compound, chemistry, Cyclic AMP, Neurites, Humans, Stem cell, Progenitor cell, Protein kinase A, Protein Kinase Inhibitors

الوصف: Human neurons derived from stem cells can be employed as in vitro models to predict the potential of neurochemicals affecting neurodevelopmental cellular processes including proliferation, migration, and differentiation. Here, we developed a model of differentiating human neurons from well characterized human embryonal carcinoma stem cells (NT2). NT2 cells were induced to differentiate into neuronal phenotypes after 2 weeks of treatment with retinoic acid in aggregate culture. Nestin positive progenitor cells migrate out of NT2 aggregates and differentiate into βIII-tubulin expressing neuronal cells. Culturing the NT2 cells for an additional 7–14 days resulted in increased percentage of βIII-tubulin expressing cells, elaborating a long neurite that positively stained for axonal marker (Tau) and presynaptic protein (synapsin). We then asked whether neurite outgrowth from NT2 cells is modulated by bioactive chemicals. Since the cAMP/PKA pathway has been widely investigated as a regulator of neurite outgrowth/regeneration in several experimental systems, we used chemical activators and inhibitors of cAMP/PKA pathway in the culture. The adenylyl cyclase activator, forskolin, and cell-permeable analog of cAMP, 8-Br-cAMP increased the percentage of neurite bearing cells and neurite extension. Application of the protein kinase A inhibitors, H-89 and Rp-cAMP, blocked neurite formation. Taken together, NT2 aggregates undergo migration, differentiation, and neurite elaboration and can be used as a model of differentiating human neurons to screen neurochemicals and to understand cellular mechanisms of human nerve cell development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c25a1590e1ad469ce15688713387ab0Test
https://pubmed.ncbi.nlm.nih.gov/21331625Test

المؤلفون: Gerd Bicker, Michael Stern, Carola Dewitz, Frank Roloff, Hannah Scheiblich, Silke Dempewolf

المصدر: PLoS ONE, Vol 10, Iss 2, p e0118536 (2015)
PLoS ONE

مصطلحات موضوعية: Nervous system, RHOA, Neurite, Cell Survival, lcsh:Medicine, Cell Line, chemistry.chemical_compound, Lysophosphatidic acid, Neurites, medicine, Humans, Axon, lcsh:Science, Protein Kinase Inhibitors, Rho-associated protein kinase, Neurons, rho-Associated Kinases, Multidisciplinary, biology, lcsh:R, Cell biology, Enzyme Activation, medicine.anatomical_structure, nervous system, chemistry, biology.protein, lcsh:Q, Neuron, Collapsin response mediator protein family, Signal Transduction, Research Article

الوصف: Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68240f5c34db58e3d126a2a996d21be3Test
https://doi.org/10.1371/journal.pone.0118536Test