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axon transport

Xin Liu, Chunkui Zhang, Qian Liu, Kaixiang Zhou, Nannan Yin, Hongyun Zhang, Minghong Shi, Xiaodong Liu, Meiqing Wang
Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)-trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA...
October 20, 2018: European Journal of Oral Sciences
Stephen Gilmore-Hall, Jennifer Kuo, Jacqueline M Ward, Rabaab Zahra, Richard S Morrison, Guy Perkins, Albert R La Spada
A perplexing question in neurodegeneration is why different neurons degenerate. The Purkinje cell degeneration ( pcd ) mouse displays a dramatic phenotype of degeneration of cerebellar Purkinje cells. Loss of CCP1/Nna1 deglutamylation of tubulin accounts for pcd neurodegeneration, but the mechanism is unknown. In this study, we modulated the dosage of fission and fusion genes in a Drosophila melanogaster loss-of-function model and found that mitochondrial fragmentation and disease phenotypes were rescued by reduced Drp1...
October 18, 2018: Journal of Cell Biology
Xue Zhang, Fei Gao, Dongdong Wang, Chao Li, Yi Fu, Wei He, Jianmin Zhang
Tau protein-a member of the microtubule-associated protein family-is a key protein involved in many neurodegenerative diseases. Tau pathology in neurodegenerative diseases is characterized by pathological tau aggregation in neurofibrillary tangles (NFTs). Diseases with this typical pathological feature are called tauopathies. Parkinson's disease (PD) was not initially considered to be a typical tauopathy. However, recent studies have demonstrated increasing evidence of tau pathology in PD. A genome-wide association (GWA) study indicated a potential association between tauopathy and sporadic PD...
2018: Frontiers in Neurology
Tatsuya Osaki, Sebastien G M Uzel, Roger D Kamm
Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease involving loss of motor neurons (MNs) and muscle atrophy, still has no effective treatment, despite much research effort. To provide a platform for testing drug candidates and investigating the pathogenesis of ALS, we developed an ALS-on-a-chip technology (i.e., an ALS motor unit) using three-dimensional skeletal muscle bundles along with induced pluripotent stem cell (iPSC)-derived and light-sensitive channelrhodopsin-2-induced MN spheroids from a patient with sporadic ALS...
October 2018: Science Advances
Annie Lee, Yusuke Hirabayashi, Seok-Kyu Kwon, Tommy L Lewis, Franck Polleux
Mitochondria play numerous critical physiological functions in neurons including ATP production, Ca2+ regulation, lipid synthesis, ROS signaling, and the ability to trigger apoptosis. Recently developed technologies, including in vivo 2-photon imaging in awake behaving mice revealed that unlike in the peripheral nervous system (PNS), mitochondrial transport decreases strikingly along the axons of adult neurons of the central nervous system (CNS). Furthermore, the improvements of genetically-encoded biosensors have enabled precise monitoring of the spatial and temporal impact of mitochondria on Ca2+ , ATP and ROS homeostasis in a compartment-specific manner...
June 2018: Current Opinion in Physiology
Alexandre Babalian, Simone Eichenberger, Alessandro Bilella, Franck Girard, Viktoria Szabolcsi, Diana Roccaro, Gonzalo Alvarez-Bolado, Chun Xu, Marco R Celio
Although connections between the orbitofrontal cortex (OFC)-the seat of high cognitive functions-the lateral hypothalamus and the periaqueductal grey (PAG) have been recognized in the past, the precise targets of the descending fibres have not been identified. In the present study, viral tracer-transport experiments revealed neurons of the lateral (LO) and the ventrolateral (VLO) OFC (homologous to part of Area 13 in primates) to project to a circumscribed region in the ventrolateral hypothalamus, namely, the horizontally oriented, cylindrical parvalbumin- and Foxb1-expressing (parvafox) nucleus...
October 12, 2018: Brain Structure & Function
Chih-Wei Chen, Yu-Fei Peng, Ying-Cheng Yen, Prerana Bhan, Muniesh Muthaiyan Shanmugam, Dieter R Klopfenstein, Oliver I Wagner
Bidirectional cargo transport in neurons can be explained by two models: the "tug-of-war model" for short-range transport, in which several kinesin and dynein motors are bound to the same cargo but travel in opposing directions, and by the "motor coordination model" for long-range transport, in which small adaptors or the cargo itself activates or deactivates opposing motors. Direct interactions between the major axonal transporter kinesin-3 UNC-104(KIF1A) and the dynein/dynactin complex remains unknown...
October 12, 2018: Journal of Neuroscience Research
Lloyd T Elliott, Kevin Sharp, Fidel Alfaro-Almagro, Sinan Shi, Karla L Miller, Gwenaëlle Douaud, Jonathan Marchini, Stephen M Smith
The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity...
October 2018: Nature
Fan Wang, Fei Liu, Wanguang Chen
Triclosan (TCS) is a broad-spectrum antibacterial agent which is widely used in various personal care products and cosmetics. It has been found that TCS affects endocrine, immune, nervous, reproductive, and developmental system. Although microRNAs (miRNAs) act a pivotal part in lots of metabolic activities, whether and how they are related to the process of TCS-induced toxicity is unknown. In the present study, TCS induced changes in miRNAs and target gene expression in male zebrafish (Danio rerio) brain, and the potential mechanism was studied...
September 29, 2018: Chemosphere
Kumiko Hayashi, Yuta Tsuchizawa, Mitsuhiro Iwaki, Yasushi Okada
Although its importance is recently widely accepted, force measurement has been difficult in living biological systems, mainly due to the lack of the versatile non-invasive force measurement methods. The fluctuation theorem, which represents the thermodynamic properties of small fluctuating non-equilibrium systems, has been applied to the analysis of the thermodynamic properties of motor proteins in vitro. Here, we extend it to the axonal transport (displacement) of endosomes. The distribution of the displacement fluctuation had three or four distinct peaks around multiples of a unit value, which the fluctuation theorem can convert into the drag force exerted on the endosomes...
October 3, 2018: Molecular Biology of the Cell
Fu-Xing Zhang, Shun-Nan Ge, Yu-Lin Dong, Juan Shi, Yu-Peng Feng, Yang Li, Yun-Qing Li, Jin-Lian Li
In nervous system, glutamate transmission is crucial for centripetal conveyance and cortical perception of sensory signals of different modalities, which necessitates vesicular glutamate transporters 1-3 (VGLUT1-3), the three homologous membrane-bound protein isoforms, to load glutamate into the presysnaptic vesicles. These VGLUTs, especially VGLUT1 and VGLUT2, selectively label and define functionally distinct neuronal subpopulations at each relay level of the neural hierarchies comprising spinal and trigeminal sensory systems...
September 28, 2018: Progress in Neurobiology
Marcello Melone, Chiara Ciriachi, Daniela Pietrobon, Fiorenzo Conti
GLT-1, the major glutamate transporter, is expressed at perisynaptic astrocytic processes (PAP) and axon terminals (AxT). GLT-1 is coupled to Na+/K+-ATPase (NKA) α1-3 isoforms, whose subcellular distribution and spatial organization in relationship to GLT-1 are largely unknown. Using several microscopy techniques, we showed that at excitatory synapses α1 and α3 are exclusively neuronal (mainly in dendrites and in some AxT), while α2 is predominantly astrocytic. GLT-1 displayed a differential colocalization with α1-3...
September 27, 2018: Cerebral Cortex
Zhisheng Ji, Guowei Zhang, Li Chen, Jiong Li, Yuhao Yang, Caihui Cha, Jifeng Zhang, Hongsheng Lin, Guoqing Guo
Changing microtubule dynamics is sufficient to alter axon and dendrite specification and development. Spastin participates in the growth and regeneration of neurites by severing microtubules into small segments, and collapsin response mediator protein 5 (CRMP5) provides structural support and serves as a track for cargo transport by promoting microtubule polymerization. Nevertheless, how spastin and CRMP5 cooperate to regulate neurite outgrowth by controlling microtubule dynamics needs to be elucidated. In our present study, spastin interacted with CRMP5 in vitro and in vivo...
September 26, 2018: Developmental Neurobiology
Benita Turner-Bridger, Maximillian Jakobs, Leila Muresan, Hovy Ho-Wai Wong, Kristian Franze, William A Harris, Christine E Holt
During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression in space and time. Different sets of mRNAs exhibit different localization patterns across the axon. However, little is known about how mRNAs move in axons or how these patterns are generated. Here, we couple molecular beacon technology with highly inclined and laminated optical sheet microscopy to image single molecules of identified endogenous mRNA in growing axons...
October 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Martin Harterink, Stacey L Edwards, Bart de Haan, Kah Wai Yau, Sander van den Heuvel, Lukas C Kapitein, Kenneth G Miller, Casper C Hoogenraad
The specific organization of the neuronal microtubule cytoskeleton in axons and dendrites is an evolutionarily conserved determinant of neuronal polarity, allowing for selective cargo sorting. However, how dendritic microtubules are organized and whether local differences influence cargo transport remains largely unknown. Here, we use live-cell imaging to systematically probe the microtubule organization in C. elegans neurons and demonstrate the contribution of distinct mechanisms in the organization of dendritic microtubules...
September 25, 2018: Journal of Cell Science
Kin-Mei Leung, Bo Lu, Hovy Ho-Wai Wong, Julie Qiaojin Lin, Benita Turner-Bridger, Christine E Holt
Guidance cues trigger fast responses in axonal growth cones such as directional turning and collapse that require local protein synthesis. An attractive cue-gradient, such as Netrin-1, triggers de novo synthesis of β-actin localized to the near-side compartment of the growth cone that promotes F-actin assembly and attractive steering. How this precise spatial asymmetry in mRNA translation arises across the small expanse of the growth cone is poorly understood. Pre-localized mRNAs in the vicinity of activated receptors could be selectively translated and/or new mRNAs could be trafficked into the area...
2018: Frontiers in Cellular Neuroscience
Bai Hui Chen, Joon Ha Park, Yun Lyul Lee, Il Jun Kang, Dae Won Kim, In Koo Hwang, Choong-Hyun Lee, Bing Chun Yan, Young-Myeong Kim, Tae-Kyeong Lee, Jae Chul Lee, Moo-Ho Won, Ji Hyeon Ahn
Vascular dementia affects cognition by damaging axons and myelin. Melatonin is pharmacologically associated with various neurological disorders. In this study, effects of melatonin on cognitive impairment and related mechanisms were investigated in an animal model of ischemic vascular dementia (IVD). Melatonin was intraperitoneally administered to adult gerbils after transient global cerebral ischemia (tGCI) for 25 days beginning 5 days after tGCI. Cognitive impairment was examined using a passive avoidance test and the Barnes maze test...
September 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sebastian Rühling, Franziska Kramer, Selina Schmutz, Sandra Amor, Zhan Jiangshan, Christoph Schmitz, Markus Kipp, Tanja Hochstrasser
Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins and organelles are as well subjected to axonal transport deficits in demyelinated tissues is not known. The aim of this study was to correlate ultrastructural morphology with the immunohistochemical appearance of acute axonal injury in a model of toxin-induced oligodendrocyte degeneration...
September 21, 2018: Molecular Neurobiology
Manmeet Singh, Reas S Khan, Kimberly Dine, Jayasri Das Sarma, Kenneth S Shindler
Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and chronic demyelination in the spinal cord and optic nerves mediated by axonal spread following intracranial inoculation in mice, with pathologic features similar to the human demyelinating disease multiple sclerosis. Spinal cord demyelination is also induced following intranasal inoculation with neurotropic MHV strains, however much higher viral doses are required as compared to intracranial inoculation. Recently, it was shown that intranasal administration of low concentrations of proteins leads to significant, rapid accumulation of protein in the optic nerve and in the eye, with only low levels reaching spinal cord and other brain regions...
2018: Frontiers in Cellular and Infection Microbiology
Mo Zhou, Muhammad Abid, Hang Yin, Hongxia Wu, Teshale Teklue, Hua-Ji Qiu, Yuan Sun
Conventional genetic engineering of pseudorabies virus (PRV) is essentially based on homologous recombination or bacterial artificial chromosome. However, these techniques require multiple plaque purification, which is labor-intensive and time-consuming. The aim of the present study was to develop an efficient, direct, and flexible genetic manipulation platform for PRV. To this end, the PRV genomic DNA was extracted from purified PRV virions and sheared into approximately 30-45-kb DNA fragments. After end-blunting and phosphorylation, the DNA fragments were separated by pulsed-field gel electrophoresis, the recovered DNA fragments were inserted into the cloning-ready fosmids...
2018: Frontiers in Microbiology
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