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https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#1
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27922548/methylcobalamin-prevents-mutant-superoxide-dismutase-1-induced-motor-neuron-death-in-vitro
#2
Shunsuke Ito, Yukina Izumi, Tetsuhiro Niidome, Yuichi Ono
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model...
December 2, 2016: Neuroreport
https://www.readbyqxmd.com/read/27921066/review-of-imaging-network-activities-in-developing-rodent-cerebral-cortex-in-vivo
#3
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
#4
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/27920424/ultrastructural-characterization-of-the-lower-motor-system-in-a-mouse-model-of-krabbe-disease
#5
Valentina Cappello, Laura Marchetti, Paola Parlanti, Silvia Landi, Ilaria Tonazzini, Marco Cecchini, Vincenzo Piazza, Mauro Gemmi
Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920150/heterotrimeric-kinesin-2-together-with-kinesin-1-steers-vesicular-acetylcholinesterase-movements-toward-the-synapse
#6
Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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/27918332/isoflurane-impairs-motor-function-recovery-by-increasing-neuroapoptosis-and-degeneration-during-spinal-ischemia-reperfusion-injury-in-rats
#8
Shih-Yuan Fang, Jung-Shun Lee, Jun-Neng Roan, Yu-Chuan Tsai, Chen-Fuh Lam
BACKGROUND: Spinal cord ischemia (SCI) leads to variable degrees of neurologic deficit in patients undergoing major cardiovascular surgery. The effect of intraoperative neuroprotection against SCI and the subsequent ischemia-reperfusion injury is still limited. Because isoflurane is a commonly used anesthetic agent during major operation, and its neuroprotective and neurotoxicity effects have both been discussed, this study aimed to investigate the effect of isoflurane on the spinal cord's functional recovery in a rat model of cord ischemia...
December 1, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#9
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/27917293/alternative-splicing-of-a-cryptic-exon-embedded-in-intron-6-of-smn1-and-smn2
#10
Satomi Yoshimoto, Nur Imma Fatimah Harahap, Yuko Hamamura, Mawaddah Ar Rochmah, Ai Shima, Naoya Morisada, Masakazu Shinohara, Toshio Saito, Kayoko Saito, Poh San Lai, Masafumi Matsuo, Hiroyuki Awano, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio
Both survival of motor neuron (SMN) genes are associated with spinal muscular atrophy; mutations in SMN1 cause the disease, and SMN2 modulates its severity. It is established that different alternative splicing of exon 7 occurs for SMN1 and SMN2, and a cryptic exon was recently found in intron 6 of both genes. Here, we characterize this cryptic exon and clarify its alternative splicing pattern in control and spinal muscular atrophy cells.
2016: Human Genome Variation
https://www.readbyqxmd.com/read/27916956/functional-diversity-of-neurotrophin-actions-on-the-oculomotor-system
#11
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/27915117/from-intentions-to-actions-neural-oscillations-encode-motor-processes-through-phase-amplitude-and-phase-amplitude-coupling
#12
Etienne Combrisson, Marcela Perrone-Bertolotti, Juan Lp Soto, Golnoush Alamian, Philippe Kahane, Jean-Philippe Lachaux, Aymeric Guillot, Karim Jerbi
Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity across widely distributed brain areas. In particular, movement initiation and execution are mediated by patterns of synchronization and desynchronization that occur concurrently across distinct frequency bands and across multiple motor cortical areas. To date, motor-related local oscillatory modulations have been predominantly examined by quantifying increases or suppressions in spectral power. However, beyond signal power, spectral properties such as phase and phase-amplitude coupling (PAC) have also been shown to carry information with regards to the oscillatory dynamics underlying motor processes...
November 30, 2016: NeuroImage
https://www.readbyqxmd.com/read/27915073/a-mathematical-model-of-reward-and-executive-circuitry-in-obsessive-compulsive-disorder
#13
Anca Raˇdulescu, Rachel Marra
The neuronal circuit that controls obsessive and compulsive behaviors involves a complex network of brain regions (some with known involvement in reward processing). Among these are cortical regions, the striatum and the thalamus (which compose the CSTC pathway), limbic areas such as the amygdala and the hippocampus, and well as dopamine pathways. Abnormal dynamic behavior in this brain network is a hallmark feature of patients with increased anxiety and motor activity, like the ones affected by OCD. There is currently no clear understanding of precisely what mechanisms generate these behaviors...
November 30, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27915043/involvement-of-bdnf-trkb-signaling-in-the-effect-of-diphenyl-diselenide-on-motor-function-in-a-parkinson-s-disease-rat-model
#14
Tuane Bazanella Sampaio, Simone Pinton, Juliana Trevisan da Rocha, Bibiana Mozzaquatro Gai, Cristina Wayne Nogueira
Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe)2] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe)2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27914942/is-there-a-role-for-ghrelin-in-central-dopaminergic-systems-focus-on-nigrostriatal-and-mesocorticolimbic-pathways
#15
REVIEW
Alicia Stievenard, Mathieu Méquinion, Zane B Andrews, Alain Destée, Marie-Christine Chartier-Harlin, Odile Viltart, Christel C Vanbesien-Mailliot
The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer. Ghrelin and its receptor, which is expressed throughout the brain, play an important role in motivation and reward. Ghrelin finely modulates the mesencephalic dopaminergic signaling and is thus currently studied in pathological conditions including dopamine-related disorders...
November 30, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27914882/representation-of-the-body-in-the-lateral-striatum-of-the-freely-moving-rat-fast-spiking-interneurons-respond-to-stimulation-of-individual-body-parts
#16
Julianna Kulik, Anthony Pawlak, Manraj Kalkat, Kevin Coffey, Mark O West
: Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts...
November 30, 2016: Brain Research
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
#17
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/27911893/the-mitochondrial-m-aaa-protease-prevents-demyelination-and-hair-greying
#18
Shuaiyu Wang, Julie Jacquemyn, Sara Murru, Paola Martinelli, Esther Barth, Thomas Langer, Carien M Niessen, Elena I Rugarli
The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27911337/effect-of-the-butyrate-prodrug-pivaloyloxymethyl-butyrate-an9-on-a-mouse-model-for-spinal-muscular-atrophy
#19
Jonathan D Edwards, Matthew E R Butchbach
Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27911332/type-0-spinal-muscular-atrophy-further%C3%A2-delineation-of-prenatal-and%C3%A2-postnatal-features-in-16-patients
#20
Sarah Grotto, Jean-Marie Cuisset, Stéphane Marret, Séverine Drunat, Patricia Faure, Séverine Audebert-Bellanger, Isabelle Desguerre, Vincent Flurin, Anne-Gaëlle Grebille, Anne-Marie Guerrot, Hubert Journel, Gilles Morin, Ghislaine Plessis, Sylvain Renolleau, Joëlle Roume, Brigitte Simon-Bouy, Renaud Touraine, Marjolaine Willems, Thierry Frébourg, Eric Verspyck, Pascale Saugier-Veber
BACKGROUND: Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. OBJECTIVE: The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype. METHODS: SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database...
November 29, 2016: Journal of Neuromuscular Diseases
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