The Experts below are selected from a list of 70035 Experts worldwide ranked by ideXlab platform
David A Greenberg - One of the best experts on this subject based on the ideXlab platform.
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neuroglobin attenuates β amyloid neurotoxicity in vitro and transgenic alzheimer phenotype in vivo
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Adil A Khan, Surita Banwait, David A GreenbergAbstract:Neuroglobin (Ngb), a vertebrate globin expressed primarily in Neurons, is induced by and protects against Neuronal hypoxia and cerebral ischemia. To investigate the spectrum and mechanism of Ngb's neuroprotective action, we studied the effect of transgenic overexpression of Ngb on NMDA and β-amyloid (Aβ) toxicity in murine Cortical Neuron cultures in vitro and on the phenotype of Alzheimer's disease (AD) transgenic (APPSw,Ind) mice. Compared with Cortical Neuron cultures from wild-type mice, cultures from Ngb-overexpressing transgenic (Ngb-Tg mice) were resistant to the toxic effects of NMDA and Aβ(25–35), as measured by polarization of cell membrane lipid rafts, mitochondrial aggregation, lactate dehydrogenase release, and nuclear fragmentation. In addition, compared with APPSw,Ind mice, double-transgenic (Ngb-Tg × APPSw,Ind) mice showed reductions in thioflavin-S-stained extracellular Aβ deposits, decreased levels of Aβ(1–40) and Aβ(1–42), and improved behavioral performance in a Y-maze test of spontaneous alternations. These findings suggest that the spectrum of Ngb's neuroprotective action extends beyond hypoxic–ischemic insults. Ngb may protect Neurons from NMDA and Aβ toxicity by inhibiting the formation of a death-signaling membrane complex, and interventions that increase Ngb expression could have therapeutic application in AD and other neurodegenerative disorders.
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vascular endothelial growth factor promotes proliferation of Cortical Neuron precursors by regulating e2f expression
The FASEB Journal, 2003Co-Authors: Yonghua Zhu, Kunlin Jin, Xiao Ou Mao, David A GreenbergAbstract:Neurogenesis, or the production of new Neurons, is regulated by physiological and pathological processes including aging, stress, and brain injury. Many mitogenic and trophic factors that regulate proliferation of nonNeuronal cells are also involved in neurogenesis. These include vascular endothelial cell growth factor (VEGF), which stimulates the incorporation of bromodeoxyuridine (BrdU) into Neuronal precursor cells in vitro and in the adult rat brain in vivo. Using BrdU labeling as an index of cell proliferation, we found that the in vitro neuroproliferative effect of VEGF was associated with up-regulation of E2F family transcription factors, cyclin D1, cyclin E, and cdc25. VEGF also increased nuclear expression of E2F1, E2F2, and E2F3, consistent with regulation of the G1/S phase transition of the cell cycle. The proliferative effect of VEGF was inhibited by the extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059, the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) ...
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endocannabinoids protect cerebral Cortical Neurons from in vitro ischemia in rats
Neuroscience Letters, 2000Co-Authors: Amy D Sinor, Stacy M Irvin, David A GreenbergAbstract:Abstract The endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonylglycerol increased cell viability in cerebral Cortical Neuron cultures subjected to 8 h of hypoxia and glucose deprivation. This effect was observed at nanomolar concentrations, was reproduced by a non-hydrolyzable analog of anandamide, and was unaltered by CB1 or CB2 cannabinoid receptor antagonists. Like synthetic cannabinoids, endocannabinoids can protect Neurons from hypoxic injury, and may represent endogenous neuroprotective molecules in cerebral ischemia.
Emilie Pacary - One of the best experts on this subject based on the ideXlab platform.
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a novel role for camkiiβ in the regulation of Cortical Neuron migration implications for neurodevelopmental disorders
Molecular Psychiatry, 2018Co-Authors: Francois Guillemot, Emilie Pacary, Olivier Nicole, Donald M Bell, Thierry Lestelasserre, Helene DoatAbstract:Perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during Neuronal development. By using in utero electroporation, we show that CaMKIIβ is an important regulator of radial migration of projection Neurons during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated migration of nascent pyramidal Neurons, whereas overexpression of CaMKIIβ inhibits migration, demonstrating that precise regulation of CaMKIIβ expression is required for correct Neuronal migration. More precisely, CaMKIIβ controls the multipolar–bipolar transition in the intermediate zone and locomotion in the Cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIβ and cofilin activities is necessary to ensure proper migration of Cortical Neurons. Thus, our findings define a novel isoform-specific function for CaMKIIβ, demonstrating that CaMKIIβ has a major biological function in the developing brain.
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an antagonistic interaction between plexinb2 and rnd3 controls rhoa activity and Cortical Neuron migration
Nature Communications, 2014Co-Authors: Roberta Azzarelli, Debbie L C Van Den Berg, Emilie Pacary, Ritu Garg, Patricia P Garcez, Philippe Riou, Anne J Ridley, Roland H Friedel, Madeline Parsons, Francois GuillemotAbstract:A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to Cortical Neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating Neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating Cortical Neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for Cortical Neuron migration.
Arnold R Kriegstein - One of the best experts on this subject based on the ideXlab platform.
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a gabaergic projection from the zona incerta to cortex promotes Cortical Neuron development
Science, 2015Co-Authors: Jiadong Chen, Arnold R KriegsteinAbstract:γ-Aminobutyric acid (GABA) is the major inhibitory transmitter in the mature brain but is excitatory in the developing cortex. We found that mouse zona incerta (ZI) projection Neurons form a GABAergic axon plexus in neonatal Cortical layer 1, making synapses with Neurons in both deep and superficial layers. A similar depolarizing GABAergic plexus exists in the developing human cortex. Selectively silencing mouse ZI GABAergic Neurons at birth decreased synaptic activity and apical dendritic complexity of Cortical Neurons. The ZI GABAergic projection becomes inhibitory with maturation and can block epileptiform activity in the adult brain. These data reveal an early-developing GABAergic projection from the ZI to Cortical layer 1 that is essential for proper development of Cortical Neurons and balances excitation with inhibition in the adult cortex.
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deriving excitatory Neurons of the neocortex from pluripotent stem cells
Neuron, 2011Co-Authors: David V Hansen, John L R Rubenstein, Arnold R KriegsteinAbstract:The human cerebral cortex is an immensely complex structure that subserves critical functions that can be disrupted in developmental and degenerative disorders. Recent innovations in cellular reprogramming and differentiation techniques have provided new ways to study the cellular components of the cerebral cortex. Here, we discuss approaches to generate specific subtypes of excitatory Cortical Neurons from pluripotent stem cells. We review spatial and temporal aspects of Cortical Neuron specification that can guide efforts to produce excitatory Neuron subtypes with increased resolution. Finally, we discuss distinguishing features of human Cortical development and their translational ramifications for Cortical stem cell technologies.
Francois Guillemot - One of the best experts on this subject based on the ideXlab platform.
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a novel role for camkiiβ in the regulation of Cortical Neuron migration implications for neurodevelopmental disorders
Molecular Psychiatry, 2018Co-Authors: Francois Guillemot, Emilie Pacary, Olivier Nicole, Donald M Bell, Thierry Lestelasserre, Helene DoatAbstract:Perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during Neuronal development. By using in utero electroporation, we show that CaMKIIβ is an important regulator of radial migration of projection Neurons during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated migration of nascent pyramidal Neurons, whereas overexpression of CaMKIIβ inhibits migration, demonstrating that precise regulation of CaMKIIβ expression is required for correct Neuronal migration. More precisely, CaMKIIβ controls the multipolar–bipolar transition in the intermediate zone and locomotion in the Cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIβ and cofilin activities is necessary to ensure proper migration of Cortical Neurons. Thus, our findings define a novel isoform-specific function for CaMKIIβ, demonstrating that CaMKIIβ has a major biological function in the developing brain.
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nipbl interacts with zfp609 and the integrator complex to regulate Cortical Neuron migration
Neuron, 2017Co-Authors: Debbie L C Van Den Berg, Roberta Azzarelli, Koji Oishi, Ben Martynoga, Noelia Urban, Dick H W Dekkers, Jeroen Demmers, Francois GuillemotAbstract:Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from Cortical neural progenitors in vivo is detrimental to Neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control Cortical Neuron migration. We find that Zfp609 and Nipbl interact with the Integrator complex, which functions in RNA polymerase 2 pause release. Indeed, Zfp609 and Nipbl co-localize at gene promoters containing paused RNA polymerase 2, and Integrator similarly regulates Neuronal migration. Our data provide a rationale and mechanistic insights for the role of Nipbl in the neurological defects associated with CdLS.
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an antagonistic interaction between plexinb2 and rnd3 controls rhoa activity and Cortical Neuron migration
Nature Communications, 2014Co-Authors: Roberta Azzarelli, Debbie L C Van Den Berg, Emilie Pacary, Ritu Garg, Patricia P Garcez, Philippe Riou, Anne J Ridley, Roland H Friedel, Madeline Parsons, Francois GuillemotAbstract:A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to Cortical Neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating Neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating Cortical Neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for Cortical Neuron migration.
Daryl R Kipke - One of the best experts on this subject based on the ideXlab platform.
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using a common average reference to improve Cortical Neuron recordings from microelectrode arrays
Journal of Neurophysiology, 2009Co-Authors: Kip A Ludwig, Rachel M Miriani, Nicholas B Langhals, Michael D Joseph, David J Anderson, Daryl R KipkeAbstract:In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of Neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.
