Global ETD Search

81	MSK1 regulates homeostatic and experience-dependent synaptic plasticity Corrêa, Sonia A.L., Hunter, C.J., Palygin, O., Wauters, S.C., Martin, K.J., McKenzie, C., McKelvey, K., Morris, R.G., Pankratov, Y., Arthur, J.S., Frenguelli, B.G. January 2012 (has links) No / The ability of neurons to modulate synaptic strength underpins synaptic plasticity, learning and memory, and adaptation to sensory experience. Despite the importance of synaptic adaptation in directing, reinforcing, and revising the behavioral response to environmental influences, the cellular and molecular mechanisms underlying synaptic adaptation are far from clear. Brain-derived neurotrophic factor (BDNF) is a prime initiator of structural and functional synaptic adaptation. However, the signaling cascade activated by BDNF to initiate these adaptive changes has not been elucidated. We have previously shown that BDNF activates mitogen- and stress-activated kinase 1 (MSK1), which regulates gene transcription via the phosphorylation of both CREB and histone H3. Using mice with a kinase-dead knock-in mutation of MSK1, we now show that MSK1 is necessary for the upregulation of synaptic strength in response to environmental enrichment in vivo. Furthermore, neurons from MSK1 kinase-dead mice failed to show scaling of synaptic transmission in response to activity deprivation in vitro, a deficit that could be rescued by reintroduction of wild-type MSK1. We also show that MSK1 forms part of a BDNF- and MAPK-dependent signaling cascade required for homeostatic synaptic scaling, which likely resides in the ability of MSK1 to regulate cell surface GluA1 expression via the induction of Arc/Arg3.1. These results demonstrate that MSK1 is an integral part of a signaling pathway that underlies the adaptive response to synaptic and environmental experience. MSK1 may thus act as a key homeostat in the activity- and experience-dependent regulation of synaptic strength. Analysis of Variance Animals Brain-derived neurotrophic factor Cells Cytoskeletal proteins Dendritic spines Environment Enzyme inhibitors Excitatory postsynaptic potentials Female Gene expression regulation Green fluorescent proteins Hippocampus Homeostasis Male Mice Inbred C57BL Transgenic Nerve tissue proteins Neuronal plasticity Neurons Patch-clamp techniques Point mutation Receptors AMPA Ribosomal protein S6 kinases Signal transduction Sodium channel blockers Synapses Tetrodotoxin Time factors REF 2014
82	The mechanism mediating fast neurotransmitter release at the calyx of Held synapse / Der Mechanismus der schnellen Neurotransmitterfreisetzung an der Held Wadel, Kristian 20 October 2008 (has links) No description available. 570 Biowissenschaften Biologie Elektrophysiologie Exozytose Exzitatorischer Postsynaptischer Strom Held'sche Calyx Hirnstamm Kalzium Kalziumkanäle Kinetik Modelle Neurotransmitter Patch-Clamp Techniken Photolyse Präsynaptische Nervenendigung Ratten Synapsen Synaptische Übertragung Synaptische Vesikel Tiere Animals Brain Stem Calcium Calcium Channels Calyx of Held Electrophysiology Excitatory Postsynaptic Currents Exocytosis Kinetics Models Neurotransmitters Patch-Clamp Techniques Photolysis Presynaptic Terminals Rats Synapses Synaptic Transmission Synaptic Vesicles 42.12 42.15 42.17
83	Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration Rainey-Smith, S.R., Andersson, D.A., Williams, R.J., Rattray, Marcus January 2010 (has links) No / The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFalpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNFalpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/mL, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using fura-2-acetoxymethyl ester microfluorimetry, we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggest that TNFalpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in amyotrophic lateral sclerosis. Animals Biotinylation Blotting Western Calcium Metabolism Calcium signaling Drug effects Cell survival Drug effects Cells Cultured Excitatory amino acid agonists Toxicity Female Fluorescent antibody technique Kainic acid Antagonists & inhibitors Toxicity Mice Motor neurons Drug effects Nerve degeneration Pathology Neuroprotective agents Phosphatidylinositol 3-Kinases Pregnancy Receptors AMPA Antagonists & inhibitors Biosynthesis Genetics Receptors Cell surface Biosynthesis Receptors Tumor necrosis factor Drug effects Spectrometry Fluorescence Tumor necrosis factor-alpha Pharmacology p38 mitogen-activated protein kinases REF 2014
84	N-Methyl-D-Aspartat-Antagonisten induzierten apoptotische Zelluntergänge im Gehirn junger Ratten Miksa, Michael 06 April 2004 (has links) Der wichtigste exzitatorische Neurotransmitter Glutamat spielt eine grosse Rolle in der Gehirnentwicklung, wie neuronale Migration und Synaptogenese. Ob glutamaterge Stimulation für das Überleben entwickelnder Neuronen notwendig ist, war bislang jedoch unbekannt. Um zu untersuchen, ob eine Hemmung von Glutamatrezeptoren im unreifen Gehirn zu Neurodegeneration führt, wurden Ratten im Alter von 1 bis 31 Tagen für 24 Stunden mit dem N-Methyl-D-Aspartat-(NMDA) Glutamatrezeptorantagonisten Dizocilpin (MK801) behandelt. Die Dichte neuronaler Degeneration wurde mikroskopisch in Kupfer-Silber- und TUNEL- gefärbten Hirnschnittpräparaten ermittelt und Unterschiede mittels ANOVA analysiert (Signifikanzniveau p / The predominant excitatory neurotransmitter glutamate plays a major role in certain aspects of neural development. However, whether developing neurons depend on glutamate for survival remains unknown. To investigate if deprivation of glutamate stimulation in the immature mammalian brain causes neuronal cell death (apoptosis), rat pups aged 0 to 30 days were treated for 24 hours with dizocilpine maleate (MK801), an N-methyl-D-aspartate-(NMDA) glutamate receptor antagonist. Density of neural degeneration was evaluated by a stereological dissector method in cupric-silver and TUNEL-stained brain slices. Groups were compared by ANOVA and significance considered at p Apoptose Tier/Ratten Neuronalale Degeneration Apoptosis Animal/Rats Dizocilpine Maleate (MK801)/pharmacology Nerve Degeneration Neurons/cytology/drug effects/metabolism Receptors 610 Medizin 33 Medizin WC 6570 YG 3900 WW 4120 YG 4300 ddc:610

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