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Axonal transport

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https://www.readbyqxmd.com/read/27920150/heterotrimeric-kinesin-2-together-with-kinesin-1-steers-vesicular-acetylcholinesterase-movements-toward-the-synapse
#1
Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27916355/enhanced-serotonin-signaling-increases-intestinal-neuroplasticity
#2
Chasen J Greig, Neeru Gandotra, John J Tackett, Michaela C Bamdad, Robert A Cowles
BACKGROUND: The intestinal mucosa recovers from injury by accelerating enterocyte proliferation resulting in villus growth. A similar phenomenon is seen after massive bowel resection. Serotonin (5-HT) has been implicated as an important regulator of mucosal homeostasis by promoting growth in the epithelium. The impact of 5-HT on other components of growing villi is not known. We hypothesized that 5-HT-stimulated growth in the intestinal epithelium would be associated with growth in other components of the villus such as enteric neural axonal processes...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27910888/microtubule-stabilising-peptides-rescue-tau-phenotypes-in-vivo
#3
Shmma Quraishe, Megan Sealey, Louise Cranfield, Amritpal Mudher
The microtubule cytoskeleton is a highly dynamic, filamentous network underpinning cellular structure and function. In Alzheimer's disease, the microtubule cytoskeleton is compromised, leading to neuronal dysfunction and eventually cell death. There are currently no disease-modifying therapies to slow down or halt disease progression. However, microtubule stabilisation is a promising therapeutic strategy that is being explored. We previously investigated the disease-modifying potential of a microtubule-stabilising peptide NAP (NAPVSIPQ) in a well-established Drosophila model of tauopathy characterised by microtubule breakdown and axonal transport deficits...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#4
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#5
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27904476/impairment-of-the-nerve-growth-factor-pathway-driving-amyloid-accumulation-in-cholinergic-neurons-the-incipit-of-the-alzheimer-s-disease-story
#6
REVIEW
Viviana Triaca, Pietro Calissano
The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF) alterations in sporadic Alzheimer's disease (AD), an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN), is one of the first homeostatic systems affected in prodromal AD...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#7
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27902378/neuronal-retrograde-transport-of-borna-disease-virus-occurs-in-signaling-endosomes
#8
Caroline M Charlier, Solène Debaisieux, Charlotte Foret, Anne Thouard, Giampetro Schiavo, Daniel Gonzalez-Dunia, Cécile Evelyne Malnou
Long-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuro-invasive viruses, such as Borna Disease Virus (BDV), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. Although BDV is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. In this work, we combined different methodological approaches, such as confocal microscopy and biochemical purification of endosomes, to study BDV retrograde transport...
November 8, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27894788/neurotoxic-mechanisms-of-paclitaxel-are-local-to-the-distal-axon-and-independent-of-transport-defects
#9
Erica L Gornstein, Thomas L Schwarz
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of paclitaxel and other chemotherapeutic agents. Paclitaxel binds and stabilizes microtubules, but the cellular mechanisms that underlie paclitaxel's neurotoxic effects are not well understood. We therefore used primary cultures of adult murine dorsal root ganglion neurons, the cell type affected in patients, to examine leading hypotheses to explain paclitaxel neurotoxicity. We address the role of microtubule hyperstabilization and its downstream effects...
November 26, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27884423/alterations-in-a-unique-class-of-cortical-chandelier-cell-axon-cartridges-in-schizophrenia
#10
Brad R Rocco, Adam M DeDionisio, David A Lewis, Kenneth N Fish
BACKGROUND: The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABAA receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs...
September 29, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27883899/cut-your-losses-spastin-mediates-branch-specific-axon-loss
#11
Hagar Meltzer, Oren Schuldiner
In this issue of Neuron, Brill et al. (2016) demonstrate that, during synapse elimination in the developing neuromuscular junction, branch-specific microtubule destabilization results in arrested axonal transport and induces axon branch loss. This process is mediated in part by the neurodegeneration-associated, microtubule-severing protein spastin.
November 23, 2016: Neuron
https://www.readbyqxmd.com/read/27876812/corrigendum-flux-of-signalling-endosomes-undergoing-axonal-retrograde-transport-is-encoded-by-presynaptic-activity-and-trkb
#12
Tong Wang, Sally Martin, Tam H Nguyen, Callista B Harper, Rachel S Gormal, Ramon Martínez-Mármol, Shanker Karunanithi, Elizabeth J Coulson, Nick R Glass, Justin J Cooper-White, Bruno van Swinderen, Frédéric A Meunier
No abstract text is available yet for this article.
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27872270/hiv-glycoprotein-gp120-impairs-fast-axonal-transport-by-activating-tak1-signaling-pathways
#13
Sarah H Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T Brady
Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27871891/long-term-alcohol-exposure-elicits-hippocampal-nonsynaptic-epileptiform-activity-changes-associated-with-expression-and-functional-changes-in-nkcc1-kcc2-co-transporters-and-na-k-atpase
#14
Luiz E C Santos, Antônio M Rodrigues, Mariana R Lopes, Victor D C Costa, Carla A Scorza, Fulvio A Scorza, Esper A Cavalheiro, Antônio-Carlos G Almeida
Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1...
November 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27870441/sexual-divergence-in-activity-dependent-neuroprotective-protein-impacting-autism-schizophrenia-and-alzheimer-s-disease
#15
REVIEW
Illana Gozes
Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) interacts with key regulatory proteins, including the chromatin remodeling complex SWI/SNF, proteins associated with RNA splicing, RNA translation, microtubule dynamics, and autophagy. ADNP regulates > 400 genes during mouse embryonic development and is essential for neural tube closure. ADNP key functions extend from mice to men, with mutations causing ADNP-related ID/autism syndrome, also known as the Helsmoortel-Van der Aa syndrome...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27866730/hereditary-neuropathies-an-update
#16
REVIEW
T Stojkovic
Hereditary neuropathies are the most common inherited neuromuscular diseases. Charcot-Marie-Tooth (CMT) disease represents the most common form with an average prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and with the advances of the latest generation sequencing, more than 80 genes have been identified. Although the common clinical phenotype comprises a progressive distal muscle weakness and sensory loss, foot deformities and decreased or absent tendon reflexes, clinical and electrophysiological phenotypes exhibit great variability...
December 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27864926/synaptic-distribution-of-individually-labeled-mitral-cells-in-the-external-plexiform-layer-of-the-mouse-olfactory-bulb
#17
Takeshi Matsuno, Emi Kiyokage, Kazunori Toida
Mitral cells are the major projection neurons of the olfactory bulb. They receive olfactory inputs, regulate information, and project their axons to the olfactory cortex. To better understand output regulation of mitral cells, we established a method to visualize individual projection neurons and quantitatively examined their synaptic distribution. Individual mitral cells were labeled by viral injection, 3D-reconstructed with light microscopy, and serial-sectioned for electron microscopy. Synaptic distributions were analyzed in electron microscopically reconstructed cell bodies, two regions of secondary dendrites (near the somata and ≈ 200 µm from the somata), and primary dendrites...
November 16, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27862607/anterograde-and-retrograde-tracing-with-high-molecular-weight-biotinylated-dextran-amine-through-thalamocortical-and-corticothalamic-pathways
#18
Wenjie Zhang, Dongsheng Xu, Jingjing Cui, Xianghong Jing, Nenggui Xu, Jianhua Liu, Wanzhu Bai
Biotinylated dextran amine (BDA) has been used for neural pathway tracing in the central nervous system for many decades, in which high molecular weight BDA appeared to be transported predominantly in the anterograde direction and less in the retrograde direction. In the current study, we reexamined the properties of neural labeling with high molecular weight BDA through a reciprocal neural pathway between thalamus and somatosensory cortex. After injection of BDA into the ventral posteromedial nucleus of thalamus (VPM) in the rat, the BDA labeling was sequentially examined on somatosensory cortex at 3, 5, 7, 10, and 14 survival days...
November 9, 2016: Microscopy Research and Technique
https://www.readbyqxmd.com/read/27861646/effect-of-geranylgeranylacetone-on-the-protection-of-retinal-ganglion-cells-in-a-mouse-model-of-normal-tension-glaucoma
#19
Zhenyu Dong, Yasuhiro Shinmei, Yoko Dong, Saori Inafuku, Junichi Fukuhara, Ryo Ando, Nobuyoshi Kitaichi, Atsuhiro Kanda, Kohichi Tanaka, Kousuke Noda, Takayuki Harada, Shinki Chin, Susumu Ishida
Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP)...
October 2016: Heliyon
https://www.readbyqxmd.com/read/27859240/the-neuroprotective-effect-of-latanoprost-acts-via-klotho-mediated-suppression-of-calpain-activation-after-optic-nerve-transection
#20
Kotaro Yamamoto, Kota Sato, Masayoshi Yukita, Masayuki Yasuda, Kazuko Omodaka, Morin Ryu, Kosuke Fujita, Koji M Nishiguchi, Shigeki Machida, Toru Nakazawa
Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of ageing phenotype: the defect of klotho gene in mice results ageing phenotype such as hypokinesis, arteriosclerosis and short lifespan...
November 15, 2016: Journal of Neurochemistry
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