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https://www.readbyqxmd.com/read/29332269/behavioral-biochemical-and-molecular-characterization-of-a-parkinson-s-disease-mouse-model-using-the-neurotoxin-2-ch3-mptp-a-novel-approach
#1
Alice Laschuk Herlinger, Agihane Rodrigues Almeida, Sarah Martins Presti-Silva, Evaldo Vitor Pereira, Filipe Andrich, Rita Gomes Wanderley Pires, Cristina Martins-Silva
The neurotoxin MPTP has long been used to create a mouse model of Parkinson's disease (PD). Indeed, several MPTP analogues have been developed, including 2'-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated...
January 13, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29331501/incorporating-upper-motor-neuron-health-in-als-drug-discovery
#2
REVIEW
Ina Dervishi, P Hande Ozdinler
Amyotrophic lateral sclerosis (ALS) is a complex disease, affecting the motor neuron circuitry. After consecutive failures in clinical trials for the past 20 years, edaravone was recently approved as the second drug for ALS. This generated excitement in the field and revealed the need to improve preclinical assays for continued success. Here, we focus on the importance and relevance of upper motor neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in preclinical assays will improve inclusion criteria for clinical trials and expedite the drug discovery effort in ALS and related motor neuron diseases...
January 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29331395/tyrosine-hydroxylase-as-a-sentinel-for-central-and-peripheral-tissue-responses-in-parkinson-s-progression-evidence-from-clinical-studies-and-neurotoxin-models
#3
REVIEW
M E Johnson, M F Salvatore, S A Maiolo, L Bobrovskaya
Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role...
January 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#4
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29330870/cell-therapy-for-spinal-cord-injury-with-olfactory-ensheathing-glia-cells-oecs
#5
REVIEW
Rosa M Gómez, Magdy Y Sánchez, Maria Portela-Lomba, Kemel Ghotme, George E Barreto, Javier Sierra, M Teresa Moreno-Flores
The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs)...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29330488/motor-skill-learning-and-reward-consumption-differentially-affect-vta-activation
#6
Susan Leemburg, Tara Canonica, Andreas Luft
Dopamine release from the ventral tegmental area (VTA) terminals in the primary motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis that dopaminergic VTA neurons projecting to M1 are activated when rewards are obtained during motor skill acquisition, but not during task execution at plateau performance, or by rewards obtained without performing skilled movements. Rats were trained to perform a skilled reaching task for 3 days (acquisition) or 7 days (plateau). In combination with retrograde labelling of VTA-to-M1 projection neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was used to assess activation of dopaminergic and non-dopaminergic VTA neurons...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330367/characterization-of-human-small-heat-shock-protein-hspb1-%C3%AE-crystallin-domain-localized-mutants-associated-with-hereditary-motor-neuron-diseases
#7
Stephen D Weeks, Lydia K Muranova, Michelle Heirbaut, Steven Beelen, Sergei V Strelkov, Nikolai B Gusev
Congenital mutations in human small heat shock protein HSPB1 (HSP27) have been linked to Charcot-Marie-Tooth disease, a commonly occurring peripheral neuropathy. Understanding the molecular mechanism of such mutations is indispensable towards developing future therapies for this currently incurable disorder. Here we describe the physico-chemical properties of the autosomal dominant HSPB1 mutants R127W, S135F and R136W. Despite having a nominal effect on thermal stability, the three mutations induce dramatic changes to quaternary structure...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330326/loss-of-balance-between-striatal-feedforward-inhibition-and-corticostriatal-excitation-leads-to-tremor
#8
Yael Oran, Izhar Bar-Gad
Fast spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats prior to and following selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum...
January 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#9
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29329693/bold-fmri-signal-in-stroke-patients-and-its-importance-for-prognosis-in-the-subacute-disease-period-preliminary-report
#10
Anetta Lasek-Bal, Joanna Kidoń, Monika Błaszczyszyn, Bartłomiej Stasiów, Amadeusz Żak
Functional magnetic resonance imaging (fMRI) allows for the assessment of neuronal activity through the blood-level-dependent signal. The purpose of study was to evaluate the pattern of brain activity in fMRI in patients with ischemic stroke and to assess the potential relationship between the activity pattern and the neurological/functional status. METHODS: The fMRI was performed in patients up to 4th day of stroke. All the patients were analyzed according to NIHSS on 1st day and mRankin scale on 14th day of stroke, followed by analyzing of fMRI signal...
December 24, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29329211/causation-of-acute-flaccid-paralysis-by-myelitis-and-myositis-in-enterovirus-d68-infected-mice-deficient-in-interferon-%C3%AE-%C3%AE-%C3%AE-receptor-deficient-mice
#11
John D Morrey, Hong Wang, Brett L Hurst, Katherine Zukor, Venkatraman Siddharthan, Arnaud J Van Wettere, Donal G Sinex, E Bart Tarbet
Enterovirus D68 (EV-D68) caused a large outbreak in the summer and fall of 2014 in the United States. It causes serious respiratory disease, but causation of associated paralysis is controversial, because the virus is not routinely identified in cerebrospinal fluid. To establish clinical correlates with human disease, we evaluated EV-D68 infection in non-lethal paralysis mouse models. Ten-day-old mice lacking interferon responses were injected intraperitoneally with the virus. Paralysis developed in hindlimbs...
January 12, 2018: Viruses
https://www.readbyqxmd.com/read/29327642/effects-of-arm-cycling-exercise-in-spinal-muscular-atrophy-type-ii-patients-a-pilot-study
#12
Gamze Bora, Şulenur Subaşı-Yıldız, Ayşe Yeşbek-Kaymaz, Numan Bulut, İpek Alemdaroğlu, Öznur Tunca-Yılmaz, Haluk Topaloğlu, Aynur Ayşe Karaduman, Hayat Erdem-Yurter
Exercise studies in neuromuscular diseases like spinal muscular atrophy (SMA), a devastating disease caused by survival of motor neuron 1 ( SMN1) gene mutations, are drawing attention due to its beneficial effects. In this study, we presented a constructed arm cycling exercise protocol and evaluated the benefits on SMA patients. Five SMA type II patients performed 12 weeks of supervised arm cycling exercise. The physical functions were evaluated together with the SMN2 copy numbers, SMN protein levels, insulin-like growth factor 1(IGF1) and binding protein 3 (IGFBP3) levels...
January 1, 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29327199/glycogen-synthase-kinase-3%C3%AE-regulates-equilibrium-between-neurogenesis-and-gliogenesis-in-rat-model-of-parkinson-s-disease-a-crosstalk-with-wnt-and-notch-signaling
#13
Sonu Singh, Akanksha Mishra, Sachi Bharti, Virendra Tiwari, Jitendra Singh, Parul, Shubha Shukla
Neurogenesis involves generation of functional newborn neurons from neural stem cells (NSCs). Insufficient formation or accelerated degeneration of newborn neurons may contribute to the severity of motor/nonmotor symptoms of Parkinson's disease (PD). However, the functional role of adult neurogenesis in PD is yet not explored and whether glycogen synthase kinase-3β (GSK-3β) affects multiple steps of adult neurogenesis in PD is still unknown. We investigated the possible underlying molecular mechanism of impaired adult neurogenesis associated with PD...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29326173/transcriptional-regulator-zeb2-is-essential-for-bergmann-glia-development
#14
Li He, Kun Yu, Fanghui Lu, Jiajia Wang, Laiman N Wu, Chuntao Zhao, Qianmei Li, Xianyao Zhou, Hanmin Liu, Dezhi Mu, Mei Xin, Mengsheng Qiu, Q Richard Lu
Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson-syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical lamination dysgenesis and locomotion defects...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29325615/inherited-dystonias-clinical-features-and-molecular-pathways
#15
Corinne E Weisheit, Samuel S Pappas, William T Dauer
Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia - a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, and selective vulnerability of distinct neuronal populations to disease mutations...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29325092/intravenous-administration-of-scaav9-hexb-normalizes-lifespan-and-prevents-pathology-in-sandhoff-disease-mice
#16
Natalia Niemir, Laura Rouvière, Aurore Besse, Marie T Vanier, Jasmin Dmytrus, Thibaut Marais, Stéphanie Astord, Jean-Philippe Puech, Ganna Panasyuk, Jonathan D Cooper, Martine Barkats, Catherine Caillaud
Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of β-hexosaminidase activity which is fatal because no effective treatment is available. A mouse model of Hexb deficiency reproduces the key pathognomonic features of SD patients with severe ubiquitous lysosomal dysfunction, GM2 accumulation, neuroinflammation and neurodegeneration, culminating in death at 4 months. Here, we show that a single intravenous neonatal administration of a self-complementary adeno-associated virus 9 vector (scAAV9) expressing the Hexb cDNA in SD mice is safe and sufficient to prevent disease development...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29324904/prohibitin-plays-a-critical-role-in-enterovirus-71-neuropathogenesis
#17
Issac Horng Khit Too, Isabelle Bonne, Eng Lee Tan, Justin Jang Hann Chu, Sylvie Alonso
A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29324456/targeted-knockdown-of-bone-morphogenetic-protein-signaling-within-neural-progenitors-protects-the-brain-and-improves-motor-function-following-postnatal-hypoxia-ischemia
#18
Robert W Dettman, Derin Birch, Augusta Fernando, John A Kessler, Maria L V Dizon
Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss...
January 12, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29323183/delivery-of-xenon-containing-echogenic-liposomes-inhibits-early-brain-injury-following-subarachnoid-hemorrhage
#19
Yi-Feng Miao, Tao Peng, Melanie R Moody, Melvin E Klegerman, Jaroslaw Aronowski, James Grotta, David D McPherson, Hyunggun Kim, Shao-Ling Huang
Xenon (Xe), a noble gas, has promising neuroprotective properties with no proven adverse side-effects. We evaluated neuroprotective effects of Xe delivered by Xe-containing echogenic liposomes (Xe-ELIP) via ultrasound-controlled cerebral drug release on early brain injury following subarachnoid hemorrhage (SAH). The Xe-ELIP structure was evaluated by ultrasound imaging, electron microscopy and gas chromatography-mass spectroscopy. Animals were randomly divided into five groups: Sham, SAH, SAH treated with Xe-ELIP, empty ELIP, or Xe-saturated saline...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323161/lack-of-fgf18-causes-abnormal-clustering-of-motor-nerve-terminals-at-the-neuromuscular-junction-with-reduced-acetylcholine-receptor-clusters
#20
Kenyu Ito, Bisei Ohkawara, Hideki Yagi, Hiroaki Nakashima, Mikito Tsushima, Kyotaro Ota, Hiroyuki Konishi, Akio Masuda, Shiro Imagama, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18-/- mice at E18...
January 11, 2018: Scientific Reports
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