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https://www.readbyqxmd.com/read/30115618/the-small-g-protein-arl8-contributes-to-lysosomal-function-and-long-range-axonal-transport-in-drosophila
#1
Cláudia Rosa-Ferreira, Sean T Sweeney, Sean Munro
The small GTPase Arl8 has emerged as a major regulatory GTPase on lysosomes. Studies in mammalian cells have shown that it regulates both fusion with late endosomes and also lysosomal motility. In its active, GTP-bound, state it recruits to lysosomes the HOPS endosomal tethering complex and also proteins that link lysosomes to microtubule motors such as the kinesin adaptor PLEKHM2. To gain further insights into Arl8 biology we examined the single Drosophila ortholog. Drosophila Arl8 is essential for viability, and mitotic clones of mutant cells are able to continue to divide but show perturbation of the late endocytic pathway...
August 16, 2018: Biology Open
https://www.readbyqxmd.com/read/30111714/tau-in-oligodendrocytes-takes-neurons-in-sickness-and-in-health
#2
REVIEW
Patrizia LoPresti
Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay breaks down, CNS degeneration follows. OLG processes are essential features for OLGs being able to connect with the neurons. As many as fifty cellular processes from a single OLG reach and wrap an equal number of axonal segments. The cellular processes extend to meet and wrap axonal segments with myelin...
August 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30104601/genes-associated-with-anhedonia-a-new-analysis-in-a-large-clinical-trial-gendep
#3
Hongyan Ren, Chiara Fabbri, Rudolf Uher, Marcella Rietschel, Ole Mors, Neven Henigsberg, Joanna Hauser, Astrid Zobel, Wolfgang Maier, Mojca Z Dernovsek, Daniel Souery, Annamaria Cattaneo, Gerome Breen, Ian W Craig, Anne E Farmer, Peter McGuffin, Cathryn M Lewis, Katherine J Aitchison
A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2...
August 13, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/30103908/diffusion-of-ca-2-from-small-boutons-en-passant-into-the-axon-shapes-ap-evoked-ca-2-transients
#4
Van Tran, Christian Stricker
Not only the amplitude but also the time course of a presynaptic Ca2+ transient determine multiple aspects of synaptic transmission. In small bouton-type synapses, the mechanisms underlying the Ca2+ decay kinetics have not been fully investigated. Here, factors that shape an action-potential-evoked Ca2+ transient were quantitatively studied in synaptic boutons of neocortical layer 5 pyramidal neurons. Ca2+ transients were measured with different concentrations of fluorescent Ca2+ indicators and analyzed based on a single-compartment model...
July 26, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/30093720/bundles-of-brain-microtubules-generate-electrical-oscillations
#5
María Del Rocío Cantero, Cecilia Villa Etchegoyen, Paula L Perez, Noelia Scarinci, Horacio F Cantiello
Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, intracellular transport, and the shape of cells. MTs also form bundles, which are particularly prominent in neurons, where they help define axons and dendrites. MTs are bio-electrochemical transistors that form nonlinear electrical transmission lines. However, the electrical properties of most MT structures remain largely unknown. Here we show that bundles of brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials...
August 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30090059/retrogradely-transportable-lentivirus-tracers-for-mapping-spinal-cord-locomotor-circuits
#6
Imran S Sheikh, Kathleen M Keefe, Noelle A Sterling, Ian P Junker, Chidubem I Eneanya, Yingpeng Liu, Xiao-Qing Tang, George M Smith
Retrograde tracing is a key facet of neuroanatomical studies involving long distance projection neurons. Previous groups have utilized a variety of tools ranging from classical chemical tracers to newer methods employing viruses for gene delivery. Here, we highlight the usage of a lentivirus that permits highly efficient retrograde transport (HiRet) from synaptic terminals within the cervical and lumbar enlargements of the spinal cord. By injecting HiRet, we can clearly identify supraspinal and propriospinal circuits innervating motor neuron pools relating to forelimb and hindlimb function...
2018: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/30086304/retrograde-degenerative-signaling-mediated-by-the-p75-neurotrophin-receptor-requires-p150-glued-deacetylation-by-axonal-hdac1
#7
Amrita Pathak, Emily M Stanley, F Edward Hickman, Natalie Wallace, Bryson Brewer, Deyu Li, Shani Gluska, Eran Perlson, Sabine Fuhrmann, Katerina Akassoglou, Francisca Bronfman, Patrizia Casaccia, Dylan T Burnette, Bruce D Carter
During development, neurons undergo apoptosis if they do not receive adequate trophic support from tissues they innervate or when detrimental factors activate the p75 neurotrophin receptor (p75NTR) at their axon ends. Trophic factor deprivation (TFD) or activation of p75NTR in distal axons results in a retrograde degenerative signal. However, the nature of this signal and the regulation of its transport are poorly understood. Here, we identify p75NTR intracellular domain (ICD) and histone deacetylase 1 (HDAC1) as part of a retrograde pro-apoptotic signal generated in response to TFD or ligand binding to p75NTR in sympathetic neurons...
August 6, 2018: Developmental Cell
https://www.readbyqxmd.com/read/30082731/phosphatidylserine-exposure-mediated-by-abc-transporter-activates-the-integrin-signaling-pathway-promoting-axon-regeneration
#8
Naoki Hisamoto, Anna Tsuge, Strahil Iv Pastuhov, Tatsuhiro Shimizu, Hiroshi Hanafusa, Kunihiro Matsumoto
Following axon injury, a cascade of signaling events is triggered to initiate axon regeneration. However, the mechanisms regulating axon regeneration are not well understood at present. In Caenorhabditis elegans, axon regeneration utilizes many of the components involved in phagocytosis, including integrin and Rac GTPase. Here, we identify the transthyretin (TTR)-like protein TTR-11 as a component functioning in axon regeneration upstream of integrin. We show that TTR-11 binds to both the extracellular domain of integrin-α and phosphatidylserine (PS)...
August 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/30081499/unraveling-the-pathways-to-neuronal-homeostasis-and-disease-mechanistic-insights-into-the-role-of-rna-binding-proteins-and-associated-factors
#9
REVIEW
Stylianos Ravanidis, Fedon-Giasin Kattan, Epaminondas Doxakis
The timing, dosage and location of gene expression are fundamental determinants of brain architectural complexity. In neurons, this is, primarily, achieved by specific sets of trans-acting RNA-binding proteins (RBPs) and their associated factors that bind to specific cis elements throughout the RNA sequence to regulate splicing, polyadenylation, stability, transport and localized translation at both axons and dendrites. Not surprisingly, misregulation of RBP expression or disruption of its function due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to the pathogenesis of several neuropsychiatric and neurodegenerative disorders such as fragile-X syndrome, autism spectrum disorders, spinal muscular atrophy, amyotrophic lateral sclerosis and frontotemporal dementia...
August 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30081192/the-multiple-functions-of-kinesin-4-family-motor-protein-kif4-and-its-clinical-potential
#10
REVIEW
Li Sheng, Shuang-Li Hao, Wan-Xi Yang, Yi Sun
Human KIF4 is a member of Kinesin-4 kinesin family. The highly conserved structure contains an N-terminal motor region, coiled-coil region and C-terminal loading region. KIF4 plays important roles in DNA repair and DNA replication, which maintains genetic stability. KIF4 is also essential for regulation of mitosis and meiosis. KIF4 cooperates with condensin I and TopoIIα to help with chromosomal condensation, and binds to a plethora of cell-cycle proteins to regulate spindle organization and cytokinesis. Additionally, KIF4 plays roles in germ plasm aggregation and radial order in germ cells...
August 3, 2018: Gene
https://www.readbyqxmd.com/read/30077796/neural-and-endocrine-regulation-of-osmoregulatory-organs-in-tick-recent-discoveries-and-implications
#11
REVIEW
Donghun Kim, Ladislav Šimo, Marie Vancová, Joshua Urban, Yoonseong Park
Ticks can survive in harsh and fluctuating vegetated environments for long durations between blood feedings with highly developed osmoregulatory mechanisms. Like the unique life history of hematophagous ticks, osmoregulatory organs and their regulatory mechanisms are significantly different from those in the closely related insect taxa. Over the last ten years, research has uncovered several neuropeptidergic innervations of the primary osmoregulatory organ, the salivary glands: myoinhibitory peptide (MIP), SIFamide, and elevenin...
August 2, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/30074297/transduction-efficacy-and-retrograde-movement-of-a-lentiviral-vector-pseudotyped-by-modified-rabies-glycoprotein-throughout-the-trisynaptic-circuit-of-the-rat-hippocampus
#12
Mostafa Farzaneh, Mohammad Sayyah, Hamid Reza Eshraghi, Negar Panahi, Hadi Mirzapour Delavar, Hamid Gholami Pourbadie
BACKGROUND: The trisynaptic circuit (entorhinal cortex--dentate gyrus--CA3--CA1) is a key uni-directional network in the hippocampus. Damages to the hippocampus interrupt this circuit and cause neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest to treat the trisynaptic circuit pathologies. METHODS: We generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG-B2. Efficiency of the vector in the retrograde transduction of the rat hippocampal neurons i...
August 3, 2018: Journal of Gene Medicine
https://www.readbyqxmd.com/read/30072881/eliminating-the-vglut2-dependent-glutamatergic-transmission-of-parvalbumin-expressing-neurons-leads-to-deficits-in-locomotion-and-vocalization-decreased-pain-sensitivity-and-increased-dominance
#13
Diana M Roccaro-Waldmeyer, Franck Girard, Daniele Milani, Elisabetta Vannoni, Laurent Prétôt, David P Wolfer, Marco R Celio
The calcium-binding protein parvalbumin (PV) is a recognized marker of short-axon GABA-ergic neurons in the cortex and the hippocampus. However in addition, PV is expressed by excitatory, glutamatergic neurons in various areas of the brain and spinal cord. Depending on the location of these neurons, loading of their synaptic vesicles with glutamate is mediated by either of three vesicular glutamate transporters (VGlut): VGlut1, VGlut2, or VGlut3. Driven by our interest in one of these glutamatergic/PV-expressing cell clusters-the lateral hypothalamic parvafox nucleus-we investigated the functions of this population of neurons by the selective deletion of VGlut2 expression in PV-expressing cells according to the Cre/Lox-approach...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/30067980/a-mutation-in-the-borcs7-subunit-of-the-lysosome-regulatory-borc-complex-results-in-motor-deficits-and-dystrophic-axonopathy-in-mice
#14
John N Snouwaert, Rachel J Church, Leigh Jania, MyTrang Nguyen, Matthew L Wheeler, Andrew Saintsing, Piotr Mieczkowski, Fernando Pardo Manuel de Villena, Diane Armao, Sheryl S Moy, Damaris N Lorenzo, Beverly H Koller
Lysosomes play a critical role in maintenance of the integrity of neuronal function, and mutations in genes that contribute to lysosome formation, transport, and activity are associated with neurodegenerative disorders. Recently, the multisubunit complex, BLOC-one-related complex (BORC), has been shown to be involved in positioning lysosomes within the cytoplasm, although the consequences of altered BORC function in adult animals have not been established. We show that a spontaneous truncation mutation in the mouse Borcs7 gene, identified through whole-genome sequencing followed by genetic complementation, results in progressive axonal dystrophy with dramatic impairment of motor function...
July 31, 2018: Cell Reports
https://www.readbyqxmd.com/read/30060007/a-quantitative-study-on-the-distribution-of-mitochondria-in-the-neuropil-of-the-juvenile-rat-somatosensory-cortex
#15
A Santuy, M Turégano-López, J R Rodríguez, L Alonso-Nanclares, J DeFelipe, A Merchán-Pérez
Mitochondria play a key role in energy production and calcium buffering, among many other functions. They provide most of the energy required by neurons, and they are transported along axons and dendrites to the regions of higher energy demands. We have used focused ion beam milling and scanning electron microscopy (FIB/SEM) to obtain stacks of serial sections from the somatosensory cortex of the juvenile rat. We have estimated the volume fraction occupied by mitochondria and their distribution between dendritic, axonal, and nonsynaptic processes...
July 27, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/30057240/extensive-transduction-and-enhanced-spread-of-a-modified-aav2-capsid-in-the-non-human-primate-cns
#16
Jerusha Naidoo, Lisa M Stanek, Kousaku Ohno, Savanah Trewman, Lluis Samaranch, Piotr Hadaczek, Catherine O'Riordan, Jennifer Sullivan, Waldy San Sebastian, John R Bringas, Christopher Snieckus, Amin Mahmoodi, Amir Mahmoodi, John Forsayeth, Krystof S Bankiewicz, Lamya S Shihabuddin
The present study was designed to characterize transduction of non-human primate brain and spinal cord with a modified adeno-associated virus serotype 2, incapable of binding to the heparan sulfate proteoglycan receptor, referred to as AAV2-HBKO. AAV2-HBKO was infused into the thalamus, intracerebroventricularly or via a combination of both intracerebroventricular and thalamic delivery. Thalamic injection of this modified vector encoding GFP resulted in widespread CNS transduction that included neurons in deep cortical layers, deep cerebellar nuclei, several subcortical regions, and motor neuron transduction in the spinal cord indicative of robust bidirectional axonal transport...
July 12, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30055413/alterations-of-functional-circuitry-in-aging-brain-and-the-impact-of-mutated-app-expression
#17
Elaine L Bearer, Brett C Manifold-Wheeler, Christopher S Medina, Aaron G Gonzales, Frances L Chaves, Russell E Jacobs
Alzheimer's disease (AD) is a disease of aging that results in cognitive impairment, dementia, and death. Pathognomonic features of AD are amyloid plaques composed of proteolytic fragments of the amyloid precursor protein (APP) and neurofibrillary tangles composed of hyperphosphorylated tau protein. One type of familial AD occurs when mutant forms of APP are inherited. Both APP and tau are components of the microtubule-based axonal transport system, which prompts the hypothesis that axonal transport is disrupted in AD, and that such disruption impacts cognitive function...
June 28, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30054789/amyotrophic-lateral-sclerosis-the-complex-path-to-precision-medicine
#18
Kevin Talbot, Emily Feneberg, Jakub Scaber, Alexander G Thompson, Martin R Turner
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the corticomotorneuronal network responsible for voluntary movement. There are well-established clinical, genetic and pathological overlaps between ALS and frontotemporal dementia (FTD), which together constitute the 'TDP-43 proteinopathies'. An ever-expanding list of genes in which mutation leads to typical ALS have implicated abnormalities in RNA processing, protein homoeostasis and axonal transport. How these apparently distinct pathways converge to cause the characteristic clinical syndrome of ALS remains unclear...
July 27, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/30054502/beyond-autophagy-a-novel-role-for-autism-linked-wdfy3-in-brain-mitophagy
#19
Eleonora Napoli, Gyu Song, Alexios Panoutsopoulos, M Asrafuzzaman Riyadh, Gaurav Kaushik, Julian Halmai, Richard Levenson, Konstantinos S Zarbalis, Cecilia Giulivi
WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3+/lacZ mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood...
July 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30050027/allogenic-fc-domain-facilitated-uptake-of-igg-in-nasal-lamina-propria-friend-or-foe-for-intranasal-cns-delivery
#20
Simone Ladel, Johannes Flamm, Arghavan Soleimani Zadeh, Dorothea Filzwieser, Julia-Christina Walter, Patrick Schlossbauer, Ralf Kinscherf, Katharina Lischka, Harald Luksch, Katharina Schindowski
BACKGROUND: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery...
July 26, 2018: Pharmaceutics
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