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Motor neurone

Antonella Sferra, Fabiana Fattori, Teresa Rizza, Elsabetta Flex, Emanuele Bellacchio, Alessandro Bruselles, Stefania Petrini, Serena Cecchetti, Massimo Teson, Fabrizia Restaldi, Andrea Ciolfi, Filippo M Santorelli, Ginevra Zanni, Sabina Barresi, Claudia Castiglioni, Marco Tartaglia, Enrico Bertini
Microtubules participate in fundamental cellular processes, including chromosomal segregation and cell division, migration, and intracellular trafficking. Their proper function is required for correct central nervous system development and operative preservation, and mutations in genes coding tubulins, the constituting units of microtubules, underlie a family of neurodevelopmental and neurodegenerative diseases, collectively known as "tubulinopathies", characterized by a wide range of neuronal defects resulting from defective proliferation, migration, and function...
March 14, 2018: Human Molecular Genetics
Rebecca L Cunningham, Kelly R Monk
In situ hybridization enables visualization of mRNA localization, and immunohistochemistry enables visualization of protein localization within a tissue or organism. Both techniques have been extensively utilized in zebrafish (Thisse et al., Development 119:1203-1215, 1993; Dutton et al., Development 128:4113-4125, 2001; Gilmour et al., Neuron 34:577-588, 2002; Lyons et al., Curr Biol 15:513-524, 2005) including for visualization of mRNA localization in Schwann cells (Lyons et al., Curr Biol 15:513-524, 2005; Monk et al...
2018: Methods in Molecular Biology
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Ghazaul Dezfuli, Richard A Gillis, Jaclyn E Tatge, Kimbell R Duncan, Kenneth L Dretchen, Patrick G Jackson, Joseph G Verbalis, Niaz Sahibzada
Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice ( Mc4r -/- ). Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r -/- mice. Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study...
2018: Frontiers in Neuroscience
Hilary C Archbold, Kasey L Jackson, Ayush Arora, Kaitlin Weskamp, Elizabeth M-H Tank, Xingli Li, Roberto Miguez, Robert D Dayton, Sharon Tamir, Ronald L Klein, Sami J Barmada
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders marked in most cases by the nuclear exclusion and cytoplasmic deposition of the RNA binding protein TDP43. We previously demonstrated that ALS-associated mutant TDP43 accumulates within the cytoplasm, and that TDP43 mislocalization predicts neurodegeneration. Here, we sought to prevent neurodegeneration in ALS/FTD models using selective inhibitor of nuclear export (SINE) compounds that target exportin-1 (XPO1)...
March 15, 2018: Scientific Reports
E M Chudinova, E S Nadezhdina
Microtubules are components of eukaryotic cytoskeleton that are involved in the transport of various components from the nucleus to the cell periphery and back. They also act as a platform for assembly of complex molecular ensembles. Ribonucleoprotein (RNP) complexes, such as ribosomes and mRNPs, are transported over significant distances (e.g. to neuronal processes) along microtubules. The association of RNPs with microtubules and their transport along these structures are essential for compartmentalization of protein biosynthesis in cells...
January 2018: Biochemistry. Biokhimii︠a︡
Lívia H Morais, Daniela B Hara, Maíra A Bicca, Anicleto Poli, Reinaldo N Takahashi
The factors that trigger the pathophysiology of Parkinson's disease (PD) are unknown. However, it is suggested that environmental factors, such as exposure to pesticides, play an important role, in addition to genetic predisposition and aging. Early signs of PD can appear in the gastrointestinal (GI) tract and in the olfactory system, preceding the onset of motor impairments by many years. The present study assessed the effects of oral rotenone administration (30 mg/kg) in inducing GI and olfactory dysfunctions associated with PD in mice...
April 2018: Behavioural Pharmacology
Guo Zhang, Wang-Ding Yuan, Ferdinand S Vilim, Elena V Romanova, Ke Yu, Si-Yuan Yin, Zi-Wei Le, Ying-Yu Xue, Ting-Ting Chen, Guo-Kai Chen, Song-An Chen, Elizabeth C Cropper, Jonathan V Sweedler, Klaudiusz R Weiss, Jian Jing
When individual neurons in a circuit contain multiple neuropeptides, these peptides can target different sets of follower neurons. This endows the circuit with a certain degree of flexibility. Here we identified a novel family of peptides, the Aplysia SPTR-Gene Family-Derived peptides (apSPTR-GF-DPs). We demonstrated apSPTR-GF-DPs, particularly apSPTR-GF-DP2, are expressed in the Aplysia CNS using immunohistochemistry and MALDI-TOF MS. apSPTR-GF-DP2 is present in single projection neurons, e.g., in the cerebral-buccal interneuron-12 (CBI-12)...
March 15, 2018: ACS Chemical Neuroscience
Kathleen S Rockland
Recent commentaries on the role of the thalamus consider a wide sphere of influence beyond sensory-motor transformation, to include task-relevant cognitive processes. In this short review, I reconsider known anatomic features of corticothalamic connectivity, primarily for macaque monkey, and discuss these as part of an intricate network architecture consistent with multiple connectional re-combinations and a diversity of functional tasks. Drawing mainly on results from single axon analysis for the two broad classes of corticothalamic (CT) connections, I review the strikingly complementary spatial parameters of their extrinsic CT arbors in relation to intrinsic cortical collaterals...
March 14, 2018: European Journal of Neuroscience
Adam J Stark, Christopher T Smith, Kalen J Petersen, Paula Trujillo, Nelleke C van Wouwe, Manus J Donahue, Robert M Kessler, Ariel Y Deutch, David H Zald, Daniel O Claassen
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited...
2018: NeuroImage: Clinical
Sara Ekmark-Lewén, Veronica Lindström, Astrid Gumucio, Elisabeth Ihse, Anish Behere, Philipp J Kahle, Eva Nordström, Maria Eriksson, Anna Erlandsson, Joakim Bergström, Martin Ingelsson
Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other α-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points...
March 2018: Brain and Behavior
Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
Jie Hao, Shuangyue Li, Xiaoxia Shi, Zhiqiang Qian, Yijie Sun, Dunjia Wang, Xueying Zhou, Hongxin Qu, Shuhai Hu, Enjun Zuo, Cong Zhang, Liyan Hou, Qingshan Wang, Fengyuan Piao
Chronic exposure to n-hexane, a widely used organic solvent in industry, induces central-peripheral neuropathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). We recently reported that transplantation of bone marrow-mesenchymal stem cells (BMSC) significantly ameliorated HD-induced neuronal damage and motor deficits in rats. However, the mechanisms remain unclear. Here, we reported that inhibition of HD-induced autophagy contributed to BMSC-afforded protection. BMSC transplantation significantly reduced the levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and the degradation of sequestosome-1 (p62) in the spinal cord and sciatic nerve of HD-intoxicated rats...
March 14, 2018: Scientific Reports
Mary E Orczykowski, Kevin R Arndt, Lauren E Palitz, Brian C Kramer, Monica A Pessina, Adrian L Oblak, Seth P Finklestein, Farzad Mortazavi, Douglas L Rosene, Tara L Moore
Stroke results in enduring damage to the brain which is accompanied by innate neurorestorative processes, such as reorganization of surviving circuits. Nevertheless, patients are often left with permanent residual impairments. Cell based therapy is an emerging therapeutic that may function to enhance the innate neurorestorative capacity of the brain. We previously evaluated human umbilical tissue-derived cells (hUTC) in our non-human primate model of cortical injury limited to the hand area of primary motor cortex...
March 11, 2018: Experimental Neurology
Eleftherios Neromyliotis, Adonis K Moschovakis
We studied the phasic saccade related discharges of single neurons (S neurons) of the premotor cortex of female rhesus monkeys, mostly in the caudal bank of the arcuate sulcus. As described in previous work from our laboratory (Neromyliotis and Moschovakis, 2017b), some of these cells emitted phasic discharges for coordinated movements of the eyes and hand as well as for movements of either effector executed in isolation (motor equivalence -Meq). Other cells (S), did not emit phasic discharges for hand movements unaccompanied by saccades...
March 14, 2018: Journal of Neurophysiology
Michela Ferrucci, Gloria Lazzeri, Marina Flaibani, Francesca Biagioni, Federica Cantini, Michele Madonna, Domenico Bucci, Fiona Limanaqi, Paola Soldani, Francesco Fornai
Counting motor neurons within the spinal cord and brainstem represents a seminal step to comprehend the anatomy and physiology of the final common pathway sourcing from the CNS. Motor neuron loss allows to assess the severity of motor neuron disorders while providing a tool to assess disease modifying effects. Counting motor neurons at first implies gold standard identification methods. In fact, motor neurons may occur within mixed nuclei housing a considerable amount of neurons other than motor neurons. In the present review, we analyse various approaches to count motor neurons emphasizing both the benefits and bias of each protocol...
March 14, 2018: Histology and Histopathology
S Kabatas, C S Demir, E Civelek, I Yilmaz, A Kircelli, C Yilmaz, Y Akyuva, E Karaoz
OBJECTIVE: This study aimed to analyze the effect of human Dental Pulp-Neural Crest Stem Cells (hDP-NCSCs) delivery on lesion site after spinal cord injury (SCI), and to observe the functional recovery after transplantation. METHODS: Neural Crest Stem Cells (NCSCs) were isolated from human Dental Pulp (hDP). The experimental rat population was divided into four groups (n = 6/24). Their behavioral motility was scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for Green Fluorescent Protein (GFP) labeled hDP-NCSCs by immunofluorescence (IF) staining...
2018: Bratislavské Lekárske Listy
Adriana Schatton, Ezequiel Mendoza, Kathrin Grube, Constance Scharff
Mutations in the transcription factors FOXP1, FOXP2 and FOXP4 affect human cognition, including language. The FoxP gene locus is evolutionarily ancient and highly conserved in its DNA-binding domain. In Drosophila melanogaster FoxP has been implicated in courtship behavior, decision making and specific types of motor-learning. Because honeybees (Apis mellifera, Am) excel at navigation and symbolic dance communication, they are a particularly suitable insect species to investigate a potential link between neural FoxP expression and cognition...
March 14, 2018: Journal of Comparative Neurology
Luke Kaplan, Athena Ierokomos, Praveen Chowdary, Zev Bryant, Bianxiao Cui
Long-distance axonal transport is critical to the maintenance and function of neurons. Robust transport is ensured by the coordinated activities of multiple molecular motors acting in a team. Conventional live-cell imaging techniques used in axonal transport studies detect this activity by visualizing the translational dynamics of a cargo. However, translational measurements are insensitive to torques induced by motor activities. By using gold nanorods and multichannel polarization microscopy, we simultaneously measure the rotational and translational dynamics for thousands of axonally transported endosomes...
March 2018: Science Advances
Robert Steger, Lauren Blachorsky, Qizong Yang, Joshua C Brumberg
The properties of specific cortical cell types enable greater understanding of how cortical microcircuits process and transmit sensory, motor, and cognitive information. Previous reports have characterized the intrinsic properties of the inverted pyramidal cell (IPC) where the most prominent dendrite is orientated towards the cortical white matter. Using whole cell patch clamp recordings from rat and mouse somatosensory cortex in conjunction with electric microstimulation of the white matter we characterized the synaptic inputs onto IPCs and the more common upright pyramidal cell (UPC) in the infragranular layers...
March 13, 2018: Somatosensory & Motor Research
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