The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Roger F. Butterworth - One of the best experts on this subject based on the ideXlab platform.
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Selective Loss of Expression of Glutamate GluR2/R3 Receptor Subunits in Cerebellar Tissue from a Patient with OlivopontoCerebellar Atrophy
Metabolic Brain Disease, 2002Co-Authors: Gregoire Dirson, Paul Desjardins, Tony Tannenberg, Peter Dodd, Roger F. ButterworthAbstract:Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem Cerebellar extracts from a patient with olivopontoCerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.
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selective loss of expression of glutamate glur2 r3 receptor subunits in Cerebellar Tissue from a patient with olivopontoCerebellar atrophy
Metabolic Brain Disease, 2002Co-Authors: Gregoire Dirson, Paul Desjardins, Tony Tannenberg, P R Dodd, Roger F. ButterworthAbstract:Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem Cerebellar extracts from a patient with olivopontoCerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.
Keiko Muguruma - One of the best experts on this subject based on the ideXlab platform.
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Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs.
Cerebellum (London England), 2017Co-Authors: Keiko MugurumaAbstract:Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that Cerebellar Tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinoCerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable Cerebellar disease.
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self organized Cerebellar Tissue from human pluripotent stem cells and its application to clinical medicine
2017Co-Authors: Keiko MugurumaAbstract:The cerebellum is a highly ordered brain structure with several well-defined types of cells, which are indispensable for motor functions. It is known that the damage of the cerebellum leads to impairments in motor and postural control. The damage is often caused by Cerebellar neurodegenerative diseases that arise sporadically or from inherited genetic defects. The investigation of the pathophysiology and the discovery of drugs for these diseases require the generation of accurate disease models. However, it has been difficult to generate them due to limited information on the human Cerebellar development and unavailability of living human Cerebellar neurons in experiments.
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self organization of polarized Cerebellar Tissue in 3d culture of human pluripotent stem cells
Cell Reports, 2015Co-Authors: Keiko Muguruma, Ayaka Nishiyama, Hideshi Kawakami, Kouichi Hashimoto, Yoshiki SasaiAbstract:During Cerebellar development, the main portion of the Cerebellar plate neuroepithelium gives birth to Purkinje cells and interneurons, whereas the rhombic lip, the germinal zone at its dorsal edge, generates granule cells and Cerebellar nuclei neurons. However, it remains elusive how these components cooperate to form the intricate Cerebellar structure. Here, we found that a polarized Cerebellar structure self-organizes in 3D human embryonic stem cell (ESC) culture. The self-organized neuroepithelium differentiates into electrophysiologically functional Purkinje cells. The addition of fibroblast growth factor 19 (FGF19) promotes spontaneous generation of dorsoventrally polarized neural-tube-like structures at the level of the cerebellum. Furthermore, addition of SDF1 and FGF19 promotes the generation of a continuous Cerebellar plate neuroepithelium with rhombic-lip-like structure at one end and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human-ESC-derived Cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.
Lazaros C. Triarhou - One of the best experts on this subject based on the ideXlab platform.
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Basic Studies on Cerebellar Tissue Transplantation
Neural Transplantation in Cerebellar Ataxia, 1997Co-Authors: Lazaros C. TriarhouAbstract:As a rule, the genesis of neuronal populations, including Purkinje cells, is concluded during embryonic life, and the regenerative capacity of the adult CNS is confined to compensatory fiber sprouting and not mitotic divisions of nerve cells.1 Therefore, neurons that die as a result of regressive processes can only be replaced by implantation after harvesting from an external source. Intracerebral grafting of developing neuroblasts into the adult pathological brain has been successfully used to replace degenerated neurons in several experimental instances.2,3 In particular, primordial Cerebellar Tissue has been shown to survive and grow after orthotopic or heterotopic implantation into the adult rodent brain. An account of these studies is presented in this chapter. Cerebellar neuron grafting has also been applied to neurological mutant mice both to create appropriate confrontations between wild-type and mutant cells in elucidating gene effects on the involved lineage and to study the structural integration of transplanted wild-type Purkinje cells into the disrupted Cerebellar loop; an account of Cerebellar transplantation studies using ataxic mouse mutants is given in chapter 7.
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The Cerebellar model of neural grafting: structural integration and functional recovery.
Brain research bulletin, 1996Co-Authors: Lazaros C. TriarhouAbstract:A synopsis is presented of the recent history of Cerebellar Tissue transplantation over the past 25 years. The properties of growth and differentiation of Cerebellar grafts placed intraocularly or intracranially are reviewed, as well as the interaction of heterotopic and orthotopic grafts with the host brain. Particular emphasis is placed on the use of ataxic mouse mutants as recipients of donor Cerebellar Tissue for the correction of their structural deficits and the functional recovery of behavioural responses.
Gregoire Dirson - One of the best experts on this subject based on the ideXlab platform.
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Selective Loss of Expression of Glutamate GluR2/R3 Receptor Subunits in Cerebellar Tissue from a Patient with OlivopontoCerebellar Atrophy
Metabolic Brain Disease, 2002Co-Authors: Gregoire Dirson, Paul Desjardins, Tony Tannenberg, Peter Dodd, Roger F. ButterworthAbstract:Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem Cerebellar extracts from a patient with olivopontoCerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.
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selective loss of expression of glutamate glur2 r3 receptor subunits in Cerebellar Tissue from a patient with olivopontoCerebellar atrophy
Metabolic Brain Disease, 2002Co-Authors: Gregoire Dirson, Paul Desjardins, Tony Tannenberg, P R Dodd, Roger F. ButterworthAbstract:Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem Cerebellar extracts from a patient with olivopontoCerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.
Joachim W Deitmer - One of the best experts on this subject based on the ideXlab platform.
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higher transport and metabolism of glucose in astrocytes compared with neurons a multiphoton study of hippocampal and Cerebellar Tissue slices
Cerebral Cortex, 2014Co-Authors: Patrick Jakoby, Elke Schmidt, Ivan Ruminot, Robin Gutierrez, Felipe L Barros, Joachim W DeitmerAbstract:Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of Cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated.