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Axonal transport

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https://www.readbyqxmd.com/read/28650256/extent-of-impaired-axoplasmic-transport-and-neurofilament-compaction-in-traumatically-injured-axon-at-various-strains-and-strain-rates
#1
Anita Singh
PRIMARY OBJECTIVE: Secondary axotomy is more prevalent than the primary axotomy and involves subtle intraaxonal changes in response to the injury leading to cytoskeletal disruptions including neurofilament (NF) misalignment and compaction, which is associated with the genesis of impaired axoplasmic transport (IAT). Recent studies have reported two differential axonal responses to injury, one associated with the cytoskeletal collapse and another with the IAT. The objective of this study was to determine the extent of IAT and early NF changes in axons that were subjected to a stretch of various degrees at different strain rates...
June 26, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28649615/imaging-parkinson-s-disease-below-the-neck
#2
Per Borghammer, Karoline Knudsen, Tatyana D Fedorova, David J Brooks
Parkinson's disease is a systemic disorder with widespread and early α-synuclein pathology in the autonomic and enteric nervous systems, which is present throughout the gastrointestinal canal prior to diagnosis. Gastrointestinal and genitourinary autonomic symptoms often predate clinical diagnosis by several years. It has been hypothesized that progressive α-synuclein aggregation is initiated in hyperbranched, non-myelinated neuron terminals, and may subsequently spread via retrograde axonal transport. This would explain why autonomic nerves are so prone to formation of α-synuclein pathology...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28645943/the-structure-of-the-tetanus-toxin-reveals-ph-mediated-domain-dynamics
#3
Geoffrey Masuyer, Julian Conrad, Pål Stenmark
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor...
June 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28641988/wavy-multistratified-amacrine-cells-in-the-monkey-retina-contain-immunoreactive-secretoneurin
#4
Andrea S Bordt, Ye Long, Nobuo Kouyama, Elizabeth S Yamada, Jens Hannibal, David W Marshak
The goals of this study were to describe the morphology, neurotransmitter content and synaptic connections of neurons in primate retinas that contain the neuropeptide secretoneurin. Amacrine cells were labeled with antibodies to secretoneurin in macaque and baboon retinas. Their processes formed three distinct plexuses in the inner plexiform layer: one in the outermost stratum, one in the center and one in the innermost stratum. In light microscopic double immunolabeling experiments, GABA was colocalized with secretoneurin in these cells, but glycine transporter 1 and Substance P were not...
June 19, 2017: Peptides
https://www.readbyqxmd.com/read/28638935/jip1-and-jip3-cooperate-to-mediate-trkb-anterograde-axonal-transport-by-activating-kinesin-1
#5
Tao Sun, Yuan Li, Ting Li, Huixian Ma, Yunyun Guo, Xingyu Jiang, Ming Hou, Shuhong Huang, Zheyu Chen
Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28638629/pathophysiology-of-copeptin-in-kidney-disease-and-hypertension
#6
REVIEW
Baris Afsar
Copeptin is derived from the cleavage of the precursor of arginine vasopressin (AVP), produced in an equimolar ratio in hypothalamus and processed during axonal transport AVP is an unstable peptide and has a short half-life of 5-20 min. Unlike AVP, copeptin is a stable molecule and can easily be measured. Recent evidence suggest that increased copeptin levels have been associated with worse outcomes in various clinical conditions including chronic kidney disease (CKD) and hypertension. In this review, the data regarding copeptin with kidney function (evaluated as glomerular filtration rate, increased albumin/protein excretion or both) and hypertension with regard to performed studies, prognosis and pathogenesis was summarised...
2017: Clinical Hypertension
https://www.readbyqxmd.com/read/28637751/ifit2-is-a-restriction-factor-in-rabies-virus-pathogenicity
#7
Benjamin M Davis, Volker Fensterl, Tessa M Lawrence, Andrew W Hudacek, Ganes C Sen, Matthias J Schnell
Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that Interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma in vitro This effect was replicated in vivo, where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type after intranasal inoculation of RABV...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28636662/differential-regulation-of-polarized-synaptic-vesicle-trafficking-and-synapse-stability-in-neural-circuit-rewiring-in-caenorhabditis-elegans
#8
Naina Kurup, Dong Yan, Karina Kono, Yishi Jin
Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28633045/mrna-transport-local-translation-in-neurons
#9
REVIEW
Caspar Glock, Maximilian Heumüller, Erin M Schuman
Neurons are amongst the most structurally complex cells and exhibit a high degree of spatial compartmentalization. Also, neurons exhibit rapid and dynamic signaling by processing information in a precise and, sometimes, spatially-restricted manner. The signaling that occurs in axons and dendrites necessitates the maintenance and modification of their local proteomes. Local translation of mRNAs into protein is one solution that neurons use to meet synaptic demand and activity. Here we review some of the key findings and recent discoveries that have shaped our understanding of local translation in neuronal function and highlight important new techniques that might pave the way for new insights...
June 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28630892/disruption-of-the-axonal-trafficking-of-tyrosine-hydroxylase-mrna-impairs-catecholamine-biosynthesis-in-the-axons-of-sympathetic-neurons
#10
Armaz Aschrafi, Anthony E Gioio, Lijin Dong, Barry B Kaplan
Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28628197/vesicular-acetylcholine-transporter-vacht-overexpression-induces-major-modifications-of-striatal-cholinergic-interneuron-morphology-and-function
#11
Helena Janickova, Vania F Prado, Marco A M Prado, Salah El Mestikawy, Véronique Bernard
Striatal cholinergic interneurons (CIN) are pivotal for the regulation of the striatal network. Acetylcholine (ACh) released by CIN is centrally involved in reward behavior as well as locomotor or cognitive functions. Recently, BAC transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2) and displaying almost 50 extra copies of the VAChT gene were used to dissect cholinergic circuit connectivity and function using optogenetic approaches...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28625595/dctn1-related-neurodegeneration-perry-syndrome-and-beyond
#12
REVIEW
Takuya Konno, Owen A Ross, Hélio A G Teive, Jarosław Sławek, Dennis W Dickson, Zbigniew K Wszolek
Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150(Glued). Dynactin is a motor protein involved in axonal transport; the p150(Glued) subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought...
June 12, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28625517/reduced-tdp-43-expression-improves-neuronal-activities-in-a-drosophila-model-of-perry-syndrome
#13
Yuka Hosaka, Tsuyoshi Inoshita, Kahori Shiba-Fukushima, Changxu Cui, Taku Arano, Yuzuru Imai, Nobutaka Hattori
Parkinsonian Perry syndrome, involving mutations in the dynein motor component dynactin or p150(Glued), is characterized by TDP-43 pathology in affected brain regions, including the substantia nigra. However, the molecular relationship between p150(Glued) and TDP-43 is largely unknown. Here, we report that a reduction in TDP-43 protein levels alleviates the synaptic defects of neurons expressing the Perry mutant p150(G50R) in Drosophila. Dopaminergic expression of p150(G50R), which decreases dopamine release, disrupts motor ability and reduces the lifespan of Drosophila...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28620838/modelling-fus-mislocalisation-in-an-in-vitro-model-of-innervated-human-muscle
#14
Sonja Prpar Mihevc, Mojca Pavlin, Simona Darovic, Marko Živin, Matej Podbregar, Boris Rogelj, Tomaz Mars
Degeneration of distal axons and neuromuscular junctions is an early feature in the pathology of amyotrophic lateral sclerosis (ALS), which culminates in motor neuron loss due to axon retraction and muscle atrophy. The complex interactions in the pathogenesis of ALS between motor neurons, muscle cells and accompanying glia require an appropriate experimental model. Here, we have defined a co-culture model based on human myotubes innervated by neurons from embryonic rat spinal cord explants to investigate the pathology and treatment of ALS...
June 15, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28620279/interleukin-6-deficiency-attenuates-retinal-ganglion-cell-axonopathy-and-glaucoma-related-vision-loss
#15
Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6(t)(m1kopf)/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28616018/collapsin-response-mediator-protein-2-plays-a-major-protective-role-in-acute-axonal-degeneration
#16
REVIEW
Jian-Nan Zhang, Jan C Koch
Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2 (CRMP2) might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28614709/cytoplasmic-dynein-transports-axonal-microtubules-in-a-polarity-sorting-manner
#17
Anand N Rao, Ankita Patil, Mark M Black, Erin M Craig, Kenneth A Myers, Howard T Yeung, Peter W Baas
Axonal microtubules are predominantly organized into a plus-end-out pattern. Here, we tested both experimentally and with computational modeling whether a motor-based polarity-sorting mechanism can explain this microtubule pattern. The posited mechanism centers on cytoplasmic dynein transporting plus-end-out and minus-end-out microtubules into and out of the axon, respectively. When cytoplasmic dynein was acutely inhibited, the bi-directional transport of microtubules in the axon was disrupted in both directions, after which minus-end-out microtubules accumulated in the axon over time...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612296/kinesin-5-blocker-monastrol-protects-against-bortezomib-induced-peripheral-neurotoxicity
#18
Ilja Bobylev, Dominik Peters, Maulik Vyas, Mohammed Barham, Ines Klein, Elke Pogge von Strandmann, Wolfram F Neiss, Helmar C Lehmann
Neurotoxicity is a relevant side effect of bortezomib treatment. Previous reports have shown that the development of peripheral neuropathy caused by anti-neoplastic agents may be a result of reduced axonal transport. Based on evidence from prior studies that the kinesin-5 inhibitor monastrol enhances axonal transport and improves neuronal regeneration, we focused on the neuroprotective role of monastrol during the chemotherapeutic treatment with bortezomib. Prolonged treatment of C57BL/6 mice with bortezomib induced a length-dependent small-fiber neuropathy with axonal atrophy and loss of sensory nerve fibers...
June 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28606925/polarity-of-varicosity-initiation-in-central-neuron-mechanosensation
#19
Yuanzheng Gu, Peter Jukkola, Qian Wang, Thomas Esparza, Yi Zhao, David Brody, Chen Gu
Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca(2+)/Na(+)-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons...
June 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28606856/antinociceptive-effect-of-botulinum-toxin-a-involves-alterations-in-ampa-receptor-expression-and-glutamate-release-in-spinal-dorsal-horn-neurons
#20
Bin Hong, LingLing Yao, Linhui Ni, Li Wang, XingYue Hu
The use of botulinum toxin A (BTX-A) for various clinical therapeutic applications is increasing. It is widely believed that peripheral therapeutic or toxic effects of BTX-A are exclusively mediated by SNAP-25 cleavage. There is growing evidence of long-distance retrograde axonal transport of BTX-A on entering the central nervous system, subsequent to a local injection of the toxin. However, the prevalence of central antinociceptive effects after BTX-A peripheral application and its underlying mechanisms are unclear...
June 10, 2017: Neuroscience
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