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https://www.readbyqxmd.com/read/29228318/microcystin-lr-induces-tau-pathology-through-b%C3%AE-degradation-via-pp2a-demethylation-and-associated-gsk-3%C3%AE-phosphorylation
#1
Yali Zhang, Jiahui Zhang, Enhao Wang, Wei Qian, Yan Fan, Ying Feng, Haimeng Yin, Yang Li, Yuning Wang, Tianli Yuan
Microcystin-LR (MC-LR) has been implicated as a potential environmental factor in Alzheimer's disease because of its potent inhibition of protein phosphatase 2A (PP2A) activity, but experimental evidence to support its detailed neurotoxic effects and their underlying mechanisms has been lacking. The present study investigated the role of PP2A catalytic subunit (PP2Ac) demethylation and its link with GSK-3β in tau hyperphosphorylation induced by MC-LR. The results showed that MC-LR treatment significantly increased demethylation of PP2Ac, with a concomitant increase in GSK-3β phosphorylation at Ser9 resulting in elevated tau hyperphosphorylation at PP2A-favorable sites in SH-SY5Y cells and rat hippocampus...
December 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29228020/transplantation-of-canine-olfactory-ensheathing-cells-producing-chondroitinase-abc-promotes-chondroitin-sulphate-proteoglycan-digestion-and-axonal-sprouting-following-spinal-cord-injury
#2
Darren Carwardine, Jonathan Prager, Jacob Neeves, Elizabeth M Muir, James Uney, Nicolas Granger, Liang-Fong Wong
Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury...
2017: PloS One
https://www.readbyqxmd.com/read/29228003/a-mig-15-jnk-1-map-kinase-cascade-opposes-rpm-1-signaling-in-synapse-formation-and-learning
#3
Oliver Crawley, Andrew C Giles, Muriel Desbois, Sudhanva Kashyap, Rayna Birnbaum, Brock Grill
The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are likely to form a new MAP kinase pathway that suppresses synapse formation defects, but not axon termination defects, in the mechanosensory neurons of rpm-1 mutants. This pathway includes: MIG-15 (MAP4K), NSY-1 (MAP3K), JKK-1 (MAP2K) and JNK-1 (MAPK)...
December 11, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29227798/histological-and-mri-markers-of-white-matter-damage-in-focal-epilepsy
#4
REVIEW
Francesco Deleo, Maria Thom, Luis Concha, Andrea Bernasconi, Boris C Bernhardt, Neda Bernasconi
Growing evidence highlights the importance of white matter in the pathogenesis of focal epilepsy. Ex vivo and post-mortem studies show pathological changes in epileptic patients in white matter myelination, axonal integrity, and cellular composition. Diffusion-weighted MRI and its analytical extensions, particularly diffusion tensor imaging (DTI), have been the most widely used technique to image the white matter in vivo for the last two decades, and have shown microstructural alterations in multiple tracts both in the vicinity and at distance from the epileptogenic focus...
November 23, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29227456/photopolymerized-microfeatures-guide-adult-spiral-ganglion-and-dorsal-root-ganglion-neurite-growth
#5
Linjing Xu, Alison E Seline, Braden Leigh, Mark Ramirez, C Allan Guymon, Marlan R Hansen
HYPOTHESIS: Microtopographical patterns generated by photopolymerization of methacrylate polymer systems will direct growth of neurites from adult neurons, including spiral ganglion neurons (SGNs). BACKGROUND: Cochlear implants (CIs) provide hearing perception to patients with severe to profound hearing loss. However, their ability to encode complex auditory stimuli is limited due, in part, to poor spatial resolution caused by spread of the electrical currents in the inner ear...
January 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29227106/hollow-silica-nanoparticles-penetrate-the-peripheral-nerve-and-enhance-the-nerve-blockade-from-tetrodotoxin
#6
Qian Liu, Claudia M Santamaria, Tuo Wei, Chao Zhao, Tianjiao Ji, Tianshe Yang, Andre Shomorony, Bruce Y Wang, Daniel S Kohane
The efficacy of tetrodotoxin (TTX), a very potent local anesthetic, is limited by its poor penetration through barriers to axonal surfaces. To address this issue, we encapsulated TTX in hollow silica nanoparticles (TTX-HSN) and injected them at the sciatic nerve in rats. TTX-HSN achieved an increased frequency of successful blocks, prolonged the duration of the block, and decreased the toxicity compared to free TTX. In animals injected with fluorescently labeled HSN, the imaging of frozen sections of nerve demonstrated that HSN could penetrate into nerve and that the penetrating ability of silica nanoparticles was highly size-dependent...
December 11, 2017: Nano Letters
https://www.readbyqxmd.com/read/29226492/molecular-mechanisms-underlying-monosynaptic-sensory-motor-circuit-development-in-the-spinal-cord
#7
REVIEW
Fumiyasu Imai, Yutaka Yoshida
Motor behaviors are precisely controlled by the integration of sensory and motor systems in the central nervous system (CNS). Proprioceptive sensory neurons, key components of the sensory system, are located in the dorsal root ganglia and project axons both centrally to the spinal cord and peripherally to muscles and tendons, communicating peripheral information about the body to the CNS. Changes in muscle length detected by muscle spindles, and tension variations in tendons conveyed by golgi tendon organs, are communicated to the CNS through group Ia/II, and Ib proprioceptive sensory afferents, respectively...
December 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29226485/immunohistologic-analysis-of-spontaneous-recurrent-laryngeal-nerve-reinnervation-in-a-rat-model
#8
Andrew J Rosko, Robbi A Kupfer, Sang S Oh, Catherine T Haring, Eva L Feldman, Norman D Hogikyan
OBJECTIVE: After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury. STUDY DESIGN: Animal study. METHODS: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis...
December 11, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29226467/axon-guidance-pathways-and-the-control-of-gene-expression
#9
REVIEW
Samantha A Russell, Greg J Bashaw
Axons need to be properly guided to their targets to form synaptic connections, and this requires interactions between highly conserved extracellular and transmembrane ligands and their cell surface receptors. The majority of studies on axon guidance signaling pathways have focused on the role of these pathways in rearranging the local cytoskeleton and plasma membrane in growth cones and axons. However, a smaller body of work has demonstrated that axon guidance signaling pathways also control gene expression via local translation and transcription...
December 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29225291/-novel-function-of-axon-guidance-molecule-as-a-regulator-of-tumor-microenvironment
#10
Hironao Nakayama, Shigeki Higashiyama
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29225029/vagus-motor-neuron-topographic-map-determined-by-parallel-mechanisms-of-hox5-expression-and-time-of-axon-initiation
#11
Gabrielle R Barsh, Adam J Isabella, Cecilia B Moens
Many networks throughout the nervous system are organized into topographic maps, where the positions of neuron cell bodies in the projecting field correspond with the positions of their axons in the target field. Previous studies of topographic map development show evidence for spatial patterning mechanisms, in which molecular determinants expressed across the projecting and target fields are matched directly in a point-to-point mapping process. Here, we describe a novel temporal mechanism of topographic map formation that depends on spatially regulated differences in the timing of axon outgrowth and functions in parallel with spatial point-to-point mapping mechanisms...
December 1, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29224279/-overexpression-of-trpv1-after-periphery-nerve-injury-attenuates-nerve-regeneration-in-rats
#12
J Bai, Y Zhang, Y F Wang, J Lan, X Q Li
Objective: To observe the effect of the expressive or functional blockage of TRPV1 on nerve regeneration after sciatic trans-section injury. Methods: AMG-517, a kind of TRPV1 inhibitor, was injected into the surrounding area of the ipsilateral lumbar dorsal root ganglia while unilateral sciatic nerve was transected. A total of 24 healthy male Sprague-Dawley rats were divided into 4 groups: control group, injury only group, injury+ AMG-517 150 μg/kg group, injury+ AMG-517 300 μg/kg group. The injury only group was injected the same volume of medium...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29223871/intensity-ratio-to-improve-black-hole-assessment-in-multiple-sclerosis
#13
Gautam Adusumilli, Kathryn Trinkaus, Peng Sun, Samantha Lancia, Jeffrey D Viox, Jie Wen, Robert T Naismith, Anne H Cross
BACKGROUND: Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions. OBJECTIVE: Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging...
December 2, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29223350/%C3%AE-6-and-%C3%AE-1-integrin-heterodimer-mediates-schwann-cell-interactions-with-axons-and-facilitates-axonal-regeneration-after-peripheral-nerve-injury
#14
In Ae Chang, Ki Joong Kim, Uk Namgung
Several isoforms of integrin subunits are expressed in Schwann cells and mediate Schwann cell interactions with axons. Here, we identify α6 and β1 integrins as heterodimeric proteins expressed in Schwann cells and define their functions in axonal regeneration. α6 and β1 integrins are induced in Schwann cells in the sciatic nerve after a crush injury, and the blocking of integrin activity by siRNA expression and by treatment with anti-integrin antibodies attenuates Schwann cell contact with cultured neurons and decreases neurite outgrowth...
December 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/29223322/systemic-administration-of-epothilone-d-improves-functional-recovery-of-walking-after-rat-spinal-cord-contusion-injury
#15
Jörg Ruschel, Frank Bradke
Central nervous system (CNS) injuries cause permanent impairments of sensorimotor functions as mature neurons fail to regenerate their severed axons. The poor intrinsic growth capacity of adult CNS neurons and the formation of an inhibitory lesion scar are key impediments to axon regeneration. Systemic administration of the microtubule stabilizing agent epothilone B promotes axon regeneration and recovery of motor function by activating the intrinsic axonal growth machinery and by reducing the inhibitory fibrotic lesion scar...
December 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29222932/a-fibers-mediate-cold-hyperalgesia-in-patients-with-oxaliplatin-induced-neuropathy
#16
Julia Forstenpointner, Violetta C Oberlojer, Dennis Naleschinski, Johanna Höper, Stephanie M Helfert, Andreas Binder, Janne Gierthmühlen, Ralf Baron
Cold hyperalgesia is a common side effect of oxaliplatin treatment; still the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin-induced acute neuropathy with (n=6) and without (n=7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A-fiber afferents in combination with quantitative sensory testing. Additionally, an interview-based questionnaire assessed the severity of symptoms and the impact on daily activities...
December 9, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29222871/myelin-extracellular-leaflet-compaction-requires-apolipoprotein-d-membrane-management-to-optimize-lysosomal-dependent-recycling-and-glycocalyx-removal
#17
Nadia García-Mateo, Raquel Pascua-Maestro, Alberto Pérez-Castellanos, Concepción Lillo, Diego Sanchez, Maria D Ganfornina
To compact the extracellular sides of myelin, an important transition must take place: from membrane sliding, while building the wraps, to membrane adhesion and water exclusion. Removal of the negatively charged glycocalyx becomes the limiting factor in such transition. What is required to initiate this membrane-zipping process? Knocking-out the Lipocalin Apolipoprotein D (ApoD), essential for lysosomal functional integrity in glial cells, results in a specific defect in myelin extracellular leaflet compaction in peripheral and central nervous system, which results in reduced conduction velocity and suboptimal behavioral outputs: motor learning is compromised...
December 9, 2017: Glia
https://www.readbyqxmd.com/read/29222800/primary-motor-neuron-culture-to-promote-cellular-viability-and-myelination
#18
Jun-Kyo Francis Suh, Sujin Hyung
A culture system that can recapitulate myelination in vitro will not only help us to better understand the mechanism of myelination and demyelination but also identify possible therapeutic interventions for treating demyelinating diseases. Here, we introduce a simple and reproducible myelination culture system using mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are plated on a feeder layer of SCs, which interact with and wrap around the axons of MNs as they differentiate in culture...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222785/neuronal-cell-morphology-in-primary-cerebellar-granule-cells-using-high-content-analysis
#19
Nicholas Radio, Steven Frank
Neurite outgrowth, one of the underlying cellular processes that defines the development and functionality of the mammalian nervous system, is also a sensitive indicator of neuronal cell health. From screening libraries of putative neurotherapeutic compounds to analyzing the millions of environmental pollutants for which we have inadequate neurotoxicity safety data, the large volume of chemical compounds that require evaluation is a major obstacle for manual imaging and analysis methods. In this context, high-content analysis (HCA) has emerged as a sensitive and accurate method for detecting changes in neuronal cell morphology within a format applicable to screening large chemical libraries...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222784/methods-for-quantitative-analysis-of-axonal-cargo-transport
#20
Matias Alloatti, Luciana Bruno, Tomas L Falzone
Neurons rely on complex axonal transport mechanisms that mediate the intracellular dynamics of proteins, vesicles, and mitochondria along their high polarized structure. The fast improvement of live imaging techniques of fluorescent cargos allowed the identification of the diverse motion properties of different transported molecules. These properties arise as the result of molecular interactions between many players involved in axonal transport. Motor proteins, microtubule tracks, cargo association, and even axonal viscosity contribute to the proper axonal dynamics of different cargos...
2018: Methods in Molecular Biology
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