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https://www.readbyqxmd.com/read/29656576/repurposing-carbamazepine-for-the-treatment-of-amyotrophic-lateral-sclerosis-in-sod1-g93a-mouse-model
#1
Jing-Jing Zhang, Qin-Ming Zhou, Sheng Chen, Wei-Dong Le
AIMS: To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model. METHODS: Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn of spinal cord were quantified by Nissl staining and SMI-32 immunostaining...
April 14, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29656361/characterization-of-the-mitochondrial-aerobic-metabolism-in-the-pre-and-perisynaptic-districts-of-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#2
Silvia Ravera, Tiziana Bonifacino, Martina Bartolucci, Marco Milanese, Elena Gallia, Francesca Provenzano, Katia Cortese, Isabella Panfoli, Giambattista Bonanno
Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease characterized by muscle wasting, weakness, and spasticity due to a progressive degeneration of cortical, brainstem, and spinal motor neurons. The etiopathological causes are still largely obscure, although astrocytes definitely play a role in neuronal damage. Several mechanisms have been proposed to concur to neurodegeneration in ALS, including mitochondrial dysfunction. We have previously shown profound modifications of glutamate release and presynaptic plasticity in the spinal cord of the SOD1 G93A mouse model of ALS...
April 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29651232/tal1-gata2a-and-gata3-have-distinct-functions-in-the-development-of-v2b-and-cerebrospinal-fluid-contacting-ka-spinal-neurons
#3
Livia A Andrzejczuk, Santanu Banerjee, Samantha J England, Christiane Voufo, Kadiah Kamara, Katharine E Lewis
Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord neurons which each have particular functional properties. While we know some of the genes expressed by each of these cell types, we do not yet know how several of these neurons are specified. Here, we investigate the functions of Tal1, Gata2a, and Gata3 transcription factors in the development of two of these populations of neurons with important roles in locomotor circuitry: V2b neurons and cerebrospinal fluid-contacting Kolmer-Agduhr (KA) neurons (also called CSF-cNs)...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29642930/neuropeptide-regulation-of-adaptive-immunity-in-the-tibia-fracture-model-of-complex-regional-pain-syndrome
#4
Wen-Wu Li, Tian-Zhi Guo, Xiaoyou Shi, Frank Birklein, Tanja Schlereth, Wade S Kingery, J David Clark
BACKGROUND: Both dysfunctional neuropeptide signaling and immune system activation are characteristic of complex regional pain syndrome (CRPS). Unknown is whether substance P (SP) or calcitonin gene-related peptide (CGRP) support autoantibody production and, consequently, nociceptive sensitization. METHODS: These experiments involved the use of a well-characterized tibia fracture model of CRPS. Mice deficient in SP expression (Tac1-/- ) and CGRP signaling (RAMP1-/- ) were used to probe the neuropeptide dependence of post-fracture sensitization and antibody production...
April 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29625589/intramuscular-transplantation-of-bone-marrow-cells-prolongs-the-lifespan-of-sod1-g93a-mice-and-modulates-expression-of-prognosis-biomarkers-of-the-disease
#5
Amaya Rando, Diego Pastor, Mari Carmen Viso-León, Anna Martínez, Raquel Manzano, Xavier Navarro, Rosario Osta, Salvador Martínez
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There is no effective treatment for ALS and stem cell therapy has arisen as a potential therapeutic approach. METHODS: SOD1 mutant mice were used to study the potential neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle. RESULTS: Bone marrow intramuscular transplants resulted in increased longevity with improved motor function and decreased motoneuron degeneration in the spinal cord...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29623941/endoplasmic-reticulum-stress-transducer-old-astrocyte-specifically-induced-substance-contributes-to-astrogliosis-after-spinal-cord-injury
#6
Atsushi Takazawa, Naosuke Kamei, Nobuo Adachi, Mitsuo Ochi
Old astrocyte specifically induced substance (OASIS) is an endoplasmic reticulum (ER) stress transducer specifically expressed in astrocytes and osteoblasts. OASIS regulates the differentiation of neural precursor cells into astrocytes in the central nervous system. This study aimed to elucidate the involvement of ER stress responses stimulated via OASIS in astrogliosis following spinal cord injury. In a mouse model of spinal cord contusion injury, OASIS mRNA and protein expression were evaluated at days 7 and 14...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29617678/increased-asics-expression-via-the-camkii-creb-pathway-in-a-novel-mouse-model-of-trigeminal-pain
#7
Yan Wang, Xiujuan Fu, Lifang Huang, Xi Wang, Zuneng Lu, Fan Zhu, Zheman Xiao
BACKGROUND/AIMS: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. METHODS: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. RESULTS: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP) in the periaqueductal grey matter...
March 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29615866/expression-pattern-of-the-aspartyl-trna-synthetase-dars-in-the-human-brain
#8
Dominik Fröhlich, Alexandra K Suchowerska, Carola Voss, Ruojie He, Ernst Wolvetang, Georg von Jonquieres, Cas Simons, Thomas Fath, Gary D Housley, Matthias Klugmann
Translation of mRNA into protein is an evolutionarily conserved, fundamental process of life. A prerequisite for translation is the accurate charging of tRNAs with their cognate amino acids, a reaction catalyzed by specific aminoacyl-tRNA synthetases. One of these enzymes is the aspartyl-tRNA synthetase DARS, which pairs aspartate with its corresponding tRNA. Missense mutations of the gene encoding DARS result in the leukodystrophy hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) with a distinct pattern of hypomyelination, motor abnormalities, and cognitive impairment...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29615863/the-d2-dopamine-receptor-interferes-with-the-protective-effect-of-the-a-2a-adenosine-receptor-on-tdp-43-mislocalization-in-experimental-models-of-motor-neuron-degeneration
#9
Chia-You Lai, Yu-Ju Liu, Hsing-Lin Lai, Hui-Mei Chen, Hung-Chi Kuo, Yu-Ping Liao, Yijuang Chern
The A2A adenosine receptor (A2A R) and D2 dopamine receptor (D2 R) are two G-protein-coupled receptors that can form dimers and negatively regulate their partners. TAR DNA-binding protein (TDP-43) is a nuclear protein that has been implicated in amyotrophic lateral sclerosis (ALS). Mislocalization of TDP-43 from the nucleus to the cytoplasm is an early step of TDP-43 proteinopathy. Our previous studies indicated that A2A R is a potential drug target for ALS because treatment with an A2A R agonist (JMF1907; a T1-11 analog) prevents reactive oxygen species (ROS)-induced TDP-43 mislocalization in a motor neuron cell line (NSC34) and delays motor impairment in a TDP-43 transgenic ALS mouse model...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29614958/the-skeletal-ontogeny-of-astatotilapia-burtoni-a-direct-developing-model-system-for-the-evolution-and-development-of-the-teleost-body-plan
#10
Joost M Woltering, Michaela Holzem, Ralf F Schneider, Vasilios Nanos, Axel Meyer
BACKGROUND: The experimental approach to the evolution and development of the vertebrate skeleton has to a large extent relied on "direct-developing" amniote model organisms, such as the mouse and the chicken. These organisms can however only be partially informative where it concerns secondarily lost features or anatomical novelties not present in their lineages. The widely used anamniotes Xenopus and zebrafish are "indirect-developing" organisms that proceed through an extended time as free-living larvae, before adopting many aspects of their adult morphology, complicating experiments at these stages, and increasing the risk for lethal pleiotropic effects using genetic strategies...
April 3, 2018: BMC Developmental Biology
https://www.readbyqxmd.com/read/29614705/identification-of-a-resilient-mouse-facial-motoneuron-population-following-target-disconnection-by-injury-or-disease
#11
Deborah O Setter, Melissa M Haulcomb, Taylor Beahrs, Rena M Meadows, Nicole D Schartz, Sara K Custer, Virginia M Sanders, Kathryn J Jones
BACKGROUND: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)...
March 25, 2018: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29604388/craniofacial-structure-alterations-of-foetuses-from-folic-acid-deficient-pregnant-mice
#12
Estela Maldonado, Yamila López, Manuel Herrera, Elena Martínez-Sanz, Concepción Martínez-Álvarez, Juliana Pérez-Miguelsanz
INTRODUCTION: Craniofacial development in mammals is a complex process that involves a coordinated series of molecular and morphogenetic events. Folic acid (FA) deficiency has historically been associated with congenital spinal cord malformations, but the effect that a maternal diet deficient in FA has on the development of other structures has been poorly explored. In the present study, the objective was to describe and quantify the alterations of craniofacial structures presented in mouse foetuses from dams fed a FA deficient (FAD) diet compared with controls that were given a regular maternal diet...
March 28, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/29604317/therapeutic-time-window-of-anti-high-mobility-group-box-1-antibody-administration-in-mouse-model-of-spinal-cord-injury
#13
Masahide Nakajo, Naohiro Uezono, Hideyuki Nakashima, Hidenori Wake, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima
Spinal cord injury (SCI) is a devastating neurologic disorder that often leads to permanent disability, and there is no effective treatment for it. High mobility group box-1 (HMGB1) is a damage-associated molecular protein that triggers sterile inflammation upon injuries. We have previously shown that two administrations of neutralizing monoclonal antibody (mAb) against HMGB1 (immediately after (0 hours) and 6 hours after) SCI dramatically improves functional recovery after SCI in mice. However, when considering clinical application, 0 hours after SCI is not practical...
March 28, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29603450/nerve-growth-factor-dependent-hyperexcitability-of-capsaicin-sensitive-bladder-afferent-neurones-in-mice-with-spinal-cord-injury
#14
Takahiro Shimizu, Tsuyoshi Majima, Takahisa Suzuki, Nobutaka Shimizu, Naoki Wada, Katsumi Kadekawa, Shun Takai, Eiichiro Takaoka, Joonbeom Kwon, Anthony J Kanai, William C de Groat, Pradeep Tyagi, Motoaki Saito, Naoki Yoshimura
Nerve growth factor (NGF) has been implicated as an important mediator to induce C-fibre bladder afferent hyperexcitability, which contributes to the emergence of neurogenic lower urinary tract dysfunction (LUTD) following spinal cord injury (SCI). In this study, we determined if NGF immunoneutralization using an anti-NGF antibody (NGF-Ab) normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fibre bladder afferent neurones in female C57BL/6 mice. The spinal cord was transected at the Th8/9 level...
March 30, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29593735/involvement-of-macrophage-inflammatory-protein-1-family-members-in-the-development-of-diabetic-neuropathy-and-their-contribution-to-effectiveness-of-morphine
#15
Ewelina Rojewska, Magdalena Zychowska, Anna Piotrowska, Grzegorz Kreiner, Irena Nalepa, Joanna Mika
Current investigations underline the important roles of C-C motif ligands in the development of neuropathic pain; however, their participation in diabetic neuropathy is still undefined. Therefore, the goal of our study was to evaluate the participation of macrophage inflammatory protein-1 (MIP-1) family members (CCL3, CCL4, CCL9) in a streptozotocin (STZ)-induced mouse model of diabetic neuropathic pain. Single intrathecal administration of each MIP-1 member (10, 100, or 500 ng/5 μl) in naïve mice evoked hypersensitivity to mechanical (von Frey test) and thermal (cold plate test) stimuli...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29590636/vangl2-disruption-alters-the-biomechanics-of-late-spinal-neurulation-leading-to-spina-bifida-in-mouse-embryos
#16
Gabriel L Galea, Oleksandr Nychyk, Matteo A Mole, Dale Moulding, Dawn Savery, Evanthia Nikolopoulou, Deborah J Henderson, Nicholas D E Greene, Andrew J Copp
Human mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in neurulation. Spinal neurulation involves rostral-to-caudal 'zippering' until completion of closure is imminent, when a caudal-to-rostral closure point, 'Closure 5', arises at the caudal-most extremity of the posterior neuropore (PNP). Here, we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE) throughout neurulation and in an increasing proportion of PNP neuroepithelial cells at late neurulation stages...
March 21, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29588252/tlqp-peptides-in-amyotrophic-lateral-sclerosis-possible-blood-biomarkers-with-a-neuroprotective-role
#17
Carla Brancia, Barbara Noli, Marina Boido, Roberta Pilleri, Andrea Boi, Roberta Puddu, Francesco Marrosu, Alessandro Vercelli, Paolo Bongioanni, Gian-Luca Ferri, Cristina Cocco
While the VGF-derived TLQP peptides have been shown to prevent neuronal apoptosis, and to act on synaptic strengthening, their involvement in Amyotrophic Lateral Sclerosis (ALS) remains unclarified. We studied human ALS patients' plasma (taken at early to late disease stages) and primary fibroblast cultures (patients vs controls), in parallel with SOD1-G93A transgenic mice (taken at pre-, early- and late symptomatic stages) and the mouse motor neuron cell line (NSC-34) treated with Sodium Arsenite (SA) to induce oxidative stress...
March 26, 2018: Neuroscience
https://www.readbyqxmd.com/read/29580900/deletion-of-the-endogenous-trkb-t1-receptor-isoform-restores-the-number-of-hippocampal-ca1-parvalbumin-positive-neurons-and-rescues-long-term-potentiation-in-pre-symptomatic-msod1-g93a-als-mice
#18
Eros Quarta, Gianluca Fulgenzi, Riccardo Bravi, Erez James Cohen, Sudhirkumar Yanpallewar, Lino Tessarollo, Diego Minciacchi
Amyotrophic lateral sclerosis (ALS) causes rapidly progressive paralysis and death within 5 years from diagnosis due to degeneration of the motor circuits. However, a significant population of ALS patients also shows cognitive impairments and progressive hippocampal pathology. Likewise, the mutant SOD1(G93A) mouse model of ALS (mSOD1), in addition to loss of spinal motor neurons, displays altered spatial behavior and hippocampal abnormalities including loss of parvalbumin-positive interneurons (PVi) and enhanced long-term potentiation (LTP)...
March 23, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29578946/the-bivalent-ligand-mcc22-potently-attenuates-nociception-in-a-murine-model-of-sickle-cell-disease
#19
Giuseppe Cataldo, Mary M Lunzer, Julie K Olson, Eyup Akgün, John D Belcher, Gregory M Vercellotti, Philip S Portoghese, Donald A Simone
Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises-induced pain can be chronic or episodic. Since analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. Thus, there is a need for the development of novel treatments for pain in SCD...
March 22, 2018: Pain
https://www.readbyqxmd.com/read/29578004/the-triple-monoamine-re-uptake-inhibitor-dov-216-303-promotes-functional-recovery-after-spinal-cord-contusion-injury-in-mice
#20
Tak-Ho Chu, Karen Cummins, Peter K Stys
Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice...
March 22, 2018: Neuroscience Letters
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