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axon transport

Yuko Kobayakawa, Katsuhisa Masaki, Ryo Yamasaki, Wataru Shiraishi, Shotaro Hayashida, Shintaro Hayashi, Koichi Okamoto, Takuya Matsushita, Jun-Ichi Kira
Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A ) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases...
2018: Frontiers in Neuroscience
Cynthia L Walker, Atsuko Uchida, Yinyun Li, Niraj Trivedi, J Daniel Fenn, Paula C Monsma, Roxanne C Lariviére, Jean-Pierre Julien, Peter Jung, Anthony Brown
Myelinated axons are constricted at nodes of Ranvier. These constrictions are important physiologically because they increase the speed of saltatory nerve conduction, but they also represent potential bottlenecks for the movement of axonally transported cargoes. One type of cargo are neurofilaments, which are abundant space-filling cytoskeletal polymers that function to increase axon caliber. Neurofilaments move bidirectionally along axons, alternating between rapid movements and prolonged pauses. Strikingly, axon constriction at nodes is accompanied by a reduction in neurofilament number that can be as much as 10-fold in the largest axons...
December 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zhihao Qi, Zhen Huang, Feng Xie, Linxi Chen
Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin-related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1-dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid β (Aβ) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1-associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)...
December 4, 2018: Journal of Cellular Physiology
Alessio Facciolà, Giuseppa Visalli, Sebastiano La Maestra, Manuela Ceccarelli, Francesco D'Aleo, Giuseppe Nunnari, Giovanni Francesco Pellicanò, Angela Di Pietro
Due to their morphological and physicochemical properties, carbon nanotubes (CNTs) enhance the structural properties of several materials and are produced in great volumes. The production and the manufacturing of CNTs-incorporated products can lead to the potential environmental release of CNTs. For these reasons, CNTs can represent a serious concern for human health. Humans are exposed to nanoparticles through inhalation, ingestion and skin uptake. After their entrance, the particles can reach the Central Nervous System (CNS) through three different pathways: the systemic, olfactory and trigeminal pathways...
November 22, 2018: Environmental Toxicology and Pharmacology
Xiulan Lai, Anthony Brown, Chuan Xue
Nerve cells are critically dependent on the transport of intracellular cargoes, which are moved by motor proteins along microtubule tracks. Impairments in this movement are thought to explain the focal accumulations of axonal cargoes and axonal swellings observed in many neurodegenerative diseases. In some cases, these diseases are caused by mutations that impair motor protein function, and genetic depletion of functional molecular motors has been shown to lead to cargo accumulations in axons. The evolution of these accumulations has been compared to the formation of traffic jams on a highway, but this idea remains largely untested...
November 28, 2018: Journal of the Royal Society, Interface
Candelaria Merino-Jiménez, Filiberto Miguel, Jessica Abigail Feria Pliego, María Elena Zetina Rosales, Fredy Cifuentes, Miguel Angel Morales
Sympathetic neurons of the rat superior cervical ganglion (SCG) can segregate their neurotransmitters and co-transmitters to separate varicosities of single axons. We have shown that transmitter segregation is a plastic phenomenon and that it is correlated with the strength of synaptic transmission. Here, we determined whether sympathetic dysfunction occurring in stress and hypertension was correlated with plastic changes of neurotransmitter segregation. We characterized the expression of the markers, L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine (ACh) transporter (VAChT) in the SCG of cold stressed and spontaneously hypertensive rats (SHR)...
2018: Frontiers in Cellular Neuroscience
Yu-Lin Bai, Yu-Si Liu, Chao Ma, Kai-Xue Wang, Jie-Sheng Chen
Sodium-ion batteries (SIBs) are generally considered as promising cheap alternatives of lithium-ion batteries for stationary renewable energy storage and have received increasing attention in recent years. The exploration of anode materials with efficient electron transportation is essential for improving the performance of SIBs. Inspired by the signal transfer mode of a neuron, we designed a composite by stringing MoS2 nanoflower (soma) with multiwall carbon nanotubes (MWCNTs) (axons). High-resolution TEM observation reveals a lattice matching growth mechanism of MoS2 nanosheets on the interface of MWCNTs and the lattice expansion of the (002) plane of MoS2 ...
November 27, 2018: ACS Nano
Jian-Hai Yin, Cong-Shan Liu, Ai-Ping Yu, Jia-Qing Yao, Yu-Juan Shen, Jian-Ping Cao
BACKGROUND/AIMS: This study aims to predict the pro-angiogenic functions of monocytic-type myeloid-derived suppressor cells (M-MDSCs) derived from mice infected with Echinococcus granulosus. METHODS: M-MDSCs were collected from Balb/c mice infected with E. granulosus and normal mice (control) and cultured in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with the cell supernatant, and angiogenesis was investigated and analysed by the Angiogenesis module of the software NIH Image J...
November 27, 2018: Cellular Physiology and Biochemistry
Swati Banerjee, Maeveen Riordan
Neurexins are well known trans-synaptic cell adhesion molecules that are required for proper synaptic development and function across species. Beyond synapse organization and function, little is known about other roles Neurexins might have in the nervous system. Here we report novel phenotypic consequences of mutations in Drosophila neurexin (dnrx), which alters axonal microtubule organization and transport. We show that dnrx mutants display phenotypic similarities with the BMP receptor wishful thinking (wit) and one of the downstream effectors, futsch, which is a known regulator of microtubule organization and stability...
November 26, 2018: Scientific Reports
Christopher K Syed, Robert H Lee
We have recently been exploring the idea that axonal transport velocity is "track and motor limited." That is, microtubule length as well as microtubule-associated obstructions interact with the number of motors attached to a specific cargo to determine average cargo velocities. We assert that "slow" and "fast" transport as they are commonly referred to in the literature are really single- versus multi-motor transport along interrupted and obstructed track. To this end, we have recently developed a cargo-level motor model that appears to readily reproduce fast and slow transport simply by altering the number of motors...
November 23, 2018: Journal of Theoretical Biology
Melissa R Mandarakas, Manoj P Menezes, Kristy J Rose, Rosemary Shy, Kate Eichinger, Maria Foscan, Timothy Estilow, Rachel Kennedy, Karen Herbert, Paula Bray, Kathryn Refshauge, Monique M Ryan, Eppie M Yiu, Michelle Farrar, Hugo Sampaio, Isabella Moroni, Emanuela Pagliano, Davide Pareyson, Sabrina W Yum, David N Herrmann, Gyula Acsadi, Michael E Shy, Joshua Burns, Oranee Sanmaneechai
Many genetic subtypes of Charcot-Marie-Tooth disease (CMT) show signs of symptomatic disease during the earliest years of life. This might be the ideal time to intervene before progression of clinical sequelae due to demyelination and axonal loss. In the absence of disease-specific clinical trial outcome measures for CMT during infancy and early childhood the aim of this study was to develop and validate a functional measure of disease severity, known as the Charcot-Marie-Tooth disease Infant Scale (CMTInfS)...
December 1, 2018: Brain: a Journal of Neurology
S N Illarioshkin, S A Klyushnikov, V A Vigont, Yu A Seliverstov, E V Kaznacheyeva
Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons...
September 2018: Biochemistry. Biokhimii︠a︡
Laura Civiero, Susanna Cogo, Alice Biosa, Elisa Greggio
Leucine-rich repeat kinase 2 (LRRK2), a complex kinase/GTPase mutated in Parkinson's disease, has been shown to physically and functionally interact with cytoskeletal-related components in different brain cells. Neurons greatly rely on a functional cytoskeleton for many homeostatic processes such as local and long-distance vesicle transport, synaptic plasticity, and dendrites/axons growth and remodeling. Here, we will review the available data linking LRRK2 and the cytoskeleton, and discuss how this may be functionally relevant for the well-established roles of LRRK2 in intracellular trafficking pathways and outgrowth of neuronal processes in health and disease conditions...
November 22, 2018: Biochemical Society Transactions
Kyung Won Kim, Ngang Heok Tang, Christopher A Piggott, Matthew G Andrusiak, Seungmee Park, Ming Zhu, Naina Kurup, Salvatore J Cherra Iii, Zilu Wu, Andrew D Chisholm, Yishi Jin
The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD+ ) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms...
November 21, 2018: ELife
Julia Saifetiarova, Manzoor A Bhat
The cerebellar cortex receives neural information from other brain regions to allow fine motor coordination and motor learning. The primary output neurons from the cerebellum are the Purkinje neurons that transmit inhibitory responses to deep cerebellar nuclei through their myelinated axons. Altered morphological organization and electrical properties of the Purkinje axons lead to detrimental changes in locomotor activity often leading to cerebellar ataxias. Two cytoskeletal scaffolding proteins Band 4.1B (4...
November 17, 2018: Journal of Neuroscience Research
Maura T Weber, John D Arena, Rui Xiao, John A Wolf, Victoria E Johnson
Diffuse axonal injury (DAI) is an important consequence of traumatic brain injury (TBI). At the moment of trauma, axons rarely disconnect, but undergo cytoskeletal disruption and transport interruption leading to protein accumulation within swellings. The amyloid precursor protein (APP) accumulates rapidly and the standard histological evaluation of axonal pathology relies upon its detection. APP+ swellings first appear as varicosities along intact axons, which can ultimately undergo secondary disconnection to leave a terminal "axon bulb" at the disconnected, proximal end...
November 16, 2018: Brain Pathology
Amy E Rumora, Giovanni LoGrasso, Julia A Haidar, Justin J Dolkowski, Stephen I Lentz, Eva L Feldman
Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Since long chain saturated fatty acids (SFAs) damage DRG neurons and medium chain SFAs are reported to improve neuronal function, we evaluated the impact of SFA chain length on mitochondrial trafficking, mitochondrial function, and apoptosis...
November 15, 2018: Journal of Lipid Research
Yan-Chu Chen, Yu-Wei Chang, Yi-Shuian Huang
Regulated local translation-whereby specific mRNAs are transported and localized in subcellular domains where they are translated in response to regional signals-allows for remote control of gene expression to concentrate proteins in subcellular compartments. Neurons are highly polarized cells with unique features favoring local control for axonal pathfinding and synaptic plasticity, which are key processes involved in constructing functional circuits in the developing brain. Neurodevelopmental disorders are caused by genetic or environmental factors that disturb the nervous system's development during prenatal and early childhood periods...
November 14, 2018: Developmental Neurobiology
Floris G Wouterlood, Sanne van Oort, Lucian Bloemhard, Nico A Flierman, Jorik Spijkerman, Christopher I Wright, Jeroen A M Beliën, Hendrik J Groenewegen
Amygdalostriatal and intra-amygdaloid fiber connectivity was studied in rats via injections of one of the tracers Phaseolus vulgaris leucoagglutinin (PHA-L) or biotinylated dextran amine (BDA) into various amygdaloid nuclei. To determine the neurotransmitter identity of labeled fibers we combined tracer detection with immunofluorescence staining, using antibodies against vesicular transporters (VTs) associated with glutamatergic (VGluT1, VGluT2) or GABAergic (VGAT) neurotransmission. High-magnification confocal laser scanning images were screened for overlap: occurrence inside tracer labeled fibers or axon terminals of immunofluorescence signal associated with one of the VTs...
November 6, 2018: Journal of Chemical Neuroanatomy
L Citrigno, A Magariello, P Pugliese, G Di Palma, F L Conforti, A Petrone, M Muglia
Kinesins are a family of proteins for anterograde transport of the molecules from the neuronal cell body and their impairment has been widely associated with neurodegeneration of the motor neurons. KIF5A gene causes autosomal dominant spastic paraplegia 10, a neurological disorder characterized by spasticity and weakness of the lower limbs (SPG10). We carried out a screening of KIF5A gene in 50 subjects affected by HSP negative to diagnostic test for SPG4, ATL1 and REEP1. We identified a novel variation p.Ile255Met in a 58-year-old man who developed progressive gait disturbance due to spastic paraparesis complicated by axonal neuropathy...
December 2018: Acta Neurologica Belgica
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