Global ETD Search

141	Loss of Perineuronal Net in ME7 Prion Disease Franklin, S.L., Love, S., Greene, J.R., Betmouni, S. January 2008 (has links) No / Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid [GABA]) inhibitory interneurons, we investigated the temporal relationships between microglial activation and loss of PN and PV-positive neurons in ME7 murine prion disease. Anesthetized C57Bl/6J mice received bilateral intracerebral microinjections of ME7-infected or normal brain homogenate into the dorsal hippocampus. Microglial activation, PrP accumulation, the number of PV-positive interneurons, and Wisteria floribunda agglutinin-positive neurons (i.e. those with an intact PN) were assessed in the ventral CA1 and subiculum at 4, 8, 12, 16, and 20 weeks postinjection. Hippocampal areas and total neuron numbers in the ventral CA1 and subiculum were also determined. Loss of PN coincided with early microglial activation and with a reduction in synaptic plasticity. No significant loss of PV-positive interneurons was observed. Our findings suggest that the substrate of the earliest synaptic and behavioral abnormalities in murine prion disease may be inflammatory microglia-mediated degradation of the PN. Animals Disease models Disease progression Encephalitis Extracellular matrix Female Gliosis Hippocampus Interneurons Mice Inbred C57BL Microglia Nerve degeneration Neural pathways Neuronal plasticity Parvalbumins Plant lectins PrPSc proteins Prion diseases Receptors N-acetylglucosamine Staining and labelling Gamma-aminobutyric acid REF 2014
142	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

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Loss of Perineuronal Net in ME7 Prion Disease

MSK1 regulates homeostatic and experience-dependent synaptic plasticity