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Motor neuron development

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https://www.readbyqxmd.com/read/27932790/motor-neurons-derived-from-als-related-mouse-ips-cells-recapitulate-pathological-features-of-als
#1
Ju-Hwang Park, Hang-Soo Park, Sunghoi Hong, Seongman Kang
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27928968/rationale-for-assessing-safety-and-efficacy-of-drug-candidates-alone-and-in-combination-with-medical-devices-the-case-study-of-spinalontm
#2
Pierre A Guertin
The aim of this review is to describe the rationale and main underlying reasons for undertaking, during clinical development, the study of drug candidates used separately and/or in combination with other technologies. To ease comprehension, reference will be made to the case of SpinalonTM, a new fixed-dose combination (FDC) product composed of levodopa/carbidopa/buspirone. This drug is capable of triggering, within minutes after a single administration orally, 45 minute- episodes of basic involuntary 'reflex' walking in paraplegic animals...
December 7, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27928963/role-of-neurotrophic-factors-in-parkinson%C3%A2-s-disease
#3
Diogo Tomé, Carla Pais Fonseca, Filipa Lopes Campos, Graça Baltazar
Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels...
December 8, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27927951/effects-of-the-selective-%C3%AE-5-gabaar-antagonist-s44819-on-excitability-in-the-human-brain-a-tms-emg-and-tms-eeg-phase-i-study
#4
Ghazaleh Darmani, Carl M Zipser, Gabriele M Böhmer, Karine Deschet, Florian Müller-Dahlhaus, Paolo Belardinelli, Matthias Schwab, Ulf Ziemann
: Alpha-5 gamma-aminobutyric acid type A receptors (α5-GABAARs) are located extrasynaptically, regulate neuronal excitability through tonic inhibition, and are fundamentally important for processes such as plasticity and learning. For example, pharmacological blockade of α5-GABAAR in mice with ischemic stroke improved recovery of function by normalizing exaggerated perilesional α5-GABAAR-dependent tonic inhibition. S44819 is a novel competitive selective antagonist of the α5-GABAAR at the GABA-binding site...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27921066/review-of-imaging-network-activities-in-developing-rodent-cerebral-cortex-in-vivo
#5
REVIEW
Heiko J Luhmann
The combination of voltage-sensitive dye imaging (VSDI) with multielectrode array (MEA) recordings in the rodent cerebral cortex in vivo allows the simultaneous analysis of large-scale network interactions and electrophysiological single-unit recordings. Using this approach, distinct patterns of spontaneous and sensory-evoked activity can be recorded in the primary somatosensory (S1) and motor cortex (M1) of newborn rats. Already at the day of birth, gamma oscillations and spindle bursts in the barrel cortex synchronize the activity of a local columnar ensemble, thereby generating an early topographic representation of the sensory periphery...
July 2017: Neurophotonics
https://www.readbyqxmd.com/read/27920668/getting-mirna-therapeutics-into-the-target-cells-for-neurodegenerative-diseases-a-mini-review
#6
REVIEW
Ming Ming Wen
miRNAs play important roles in modulating gene expression in varying cellular processes and disease pathogenesis, including neurodegenerative diseases. Several miRNAs are expressed in the brain, control brain development and are identified as important biomarkers in the pathogenesis of motor-and neuro-cognitive diseases such as Alzheimer's (AD), Huntington's and Parkinson's diseases (PD) and amyotrophic lateral sclerosis. These remarkable miRNAs could be used as diagnostic markers and therapeutic targeting potential for many stressful and untreatable progressive neurodegenerative diseases...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27919237/a-novel-ano3-variant-identified-in-a-53-year-old-woman-presenting-with-hyperkinetic-dysarthria-blepharospasm-hyperkinesias-and-complex-motor%C3%A2-tics
#7
Patrick R Blackburn, Michael T Zimmermann, Jennifer M Gass, Kimberly G Harris, Margot A Cousin, Nicole J Boczek, Owen A Ross, Eric W Klee, Paul W Brazis, Jay A Van Gerpen, Paldeep S Atwal
BACKGROUND: Cervical dystonias have a variable presentation and underlying etiology, but collectively represent the most common form of focal dystonia. There are a number of known genetic forms of dystonia (DYT1-27); however the heterogeneity of disease presentation does not always make it easy to categorize the disease by phenotype-genotype comparison. CASE PRESENTATION: In this report, we describe a 53-year-old female who presented initially with hand tremor following a total hip arthroplasty...
December 5, 2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#8
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 3, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27916956/functional-diversity-of-neurotrophin-actions-on-the-oculomotor-system
#9
REVIEW
Beatriz Benítez-Temiño, María A Davis-López de Carrizosa, Sara Morcuende, Esperanza R Matarredona, Rosa R de la Cruz, Angel M Pastor
Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase)...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27913104/d-ala2-gip-glu-pal-is-neuroprotective-in-a-chronic-parkinson-s-disease-mouse-model-and-increases-bndf-expression-while-reducing-neuroinflammation-and-lipid-peroxidation
#10
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Parkinson's disease (PD). Therefore, treatment to improve insulin resistance in T2DM may be useful for PD patients. Glucose dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family that can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. We had shown previously that D-Ala2-GIP-glu-PAL, a novel long-acting GIP analogue, can play a neuroprotective role in the PD mouse model induced by acute MPTP injection...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27909399/a-subset-of-autism-associated-genes-regulate-the-structural-stability-of-neurons
#11
REVIEW
Yu-Chih Lin, Jeannine A Frei, Michaela B C Kilander, Wenjuan Shen, Gene J Blatt
Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals' ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27907033/normalization-of-patient-identified-plasma-biomarkers-in-smn%C3%AE-7-mice-following-postnatal-smn-restoration
#12
W David Arnold, Sandra Duque, Chitra C Iyer, Phillip Zaworski, Vicki L McGovern, Shannon J Taylor, Katharine M von Herrmann, Dione T Kobayashi, Karen S Chen, Stephen J Kolb, Sergey V Paushkin, Arthur H M Burghes
INTRODUCTION AND OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function...
2016: PloS One
https://www.readbyqxmd.com/read/27906111/the-functional-significance-of-the-skeletal-muscle-clock-lessons-from-bmal1-knockout-models
#13
REVIEW
Stefano Schiaffino, Bert Blaauw, Kenneth A Dyar
The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using different Bmal1 knockout (KO) models...
October 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#14
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27897203/reducing-gabaa-mediated-inhibition-improves-forelimb-motor-function-after-focal-cortical-stroke-in-mice
#15
Claudia Alia, Cristina Spalletti, Stefano Lai, Alessandro Panarese, Silvestro Micera, Matteo Caleo
A deeper understanding of post-stroke plasticity is critical to devise more effective pharmacological and rehabilitative treatments. The GABAergic system is one of the key modulators of neuronal plasticity, and plays an important role in the control of "critical periods" during brain development. Here, we report a key role for GABAergic inhibition in functional restoration following ischemia in the adult mouse forelimb motor cortex. After stroke, the majority of cortical sites in peri-infarct areas evoked simultaneous movements of forelimb, hindlimb and tail, consistent with a loss of inhibitory signalling...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895554/systemic-radical-scavenger-treatment-of-a-mouse-model-of-rett-syndrome-merits-and-limitations-of-the-vitamin-e-derivative-trolox
#16
Oliwia A Janc, Marc A Hüser, Katharina Dietrich, Belinda Kempkes, Christiane Menzfeld, Swen Hülsmann, Michael Müller
Rett syndrome (RTT) is a severe neurodevelopmental disorder typically arising from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. The almost exclusively female Rett patients show an apparently normal development during their first 6-18 months of life. Subsequently, cognitive- and motor-impairment, hand stereotypies, loss of learned skills, epilepsy and irregular breathing manifest. Early mitochondrial impairment and oxidative challenge are considered to facilitate disease progression...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27895165/rats-with-a-missense-mutation-in-atm-display-neuroinflammation-and-neurodegeneration-subsequent-to-accumulation-of-cytosolic-dna-following-unrepaired-dna-damage
#17
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27891785/editorial-brain-malformation-surveillance-in-the-zika-era
#18
EDITORIAL
Edwin Trevathan
The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection...
November 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
https://www.readbyqxmd.com/read/27891756/motility-patterns-in-mouse-colon-gastrointestinal-dysfunction-induced-by-anticancer-chemotherapy
#19
REVIEW
N J Spencer
Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil (5-FU), a major chemotherapy treatment, has been used for decades to fight numerous types of cancers, including breast, colon, and head and neck carcinomas. Unfortunately, a large proportion of patients treated with 5-FU develop toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the side effects of 5-FU are well known, the mechanisms underlying the induction of these unpleasant symptoms are poorly understood...
December 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27882949/sumo-specific-protease-1-protects-neurons-from-apoptotic-death-during-transient-brain-ischemia-reperfusion
#20
Huijun Zhang, Yan Wang, Aoxue Zhu, Dehua Huang, Shining Deng, Jinke Cheng, Michael X Zhu, Yong Li
SUMO-specific protease 1 (SENP1) deconjugates SUMO from modified proteins. Although post-ischemic activation of SUMO conjugation was suggested to be neuroprotective against ischemia/reperfusion (I/R) injury, the function of SENP1 in this process remained unclear. Here we show that transient middle cerebral artery occlusion in mice followed by 6, 12 and 24 h reperfusion significantly enhanced SENP1 levels in the affected brain area, independent of transcription. Consistent with the increase in SENP1, the levels of SUMO1-conjugated proteins were decreased by I/R in cortical neurons of control littermate mice, but unchanged in that of animals with conditional ablation of SENP1 gene from adult principal neurons, the SENP1(flox/flox):CamKIIα-Cre (SENP1 cKO) mice...
November 24, 2016: Cell Death & Disease
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