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https://www.readbyqxmd.com/read/28428745/decreased-levels-of-foldase-and-chaperone-proteins-are-associated-with-an-early-onset-amyotrophic-lateral-sclerosis
#1
Melania Filareti, Silvia Luotti, Laura Pasetto, Mauro Pignataro, Katia Paolella, Paolo Messina, Elisabetta Pupillo, Massimiliano Filosto, Christian Lunetta, Jessica Mandrioli, Giuseppe Fuda, Andrea Calvo, Adriano Chiò, Massimo Corbo, Caterina Bendotti, Ettore Beghi, Valentina Bonetto
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28418693/validating-the-predicted-effect-of-astemizole-and-ketoconazole-using-a-drosophila-model-of-parkinson-s-disease
#2
Katarzyna Styczyńska-Soczka, Luigi Zechini, Lysimachos Zografos
Parkinson's disease is a growing threat to an ever-ageing population. Despite progress in our understanding of the molecular and cellular mechanisms underlying the disease, all therapeutics currently available only act to improve symptoms and do not stop the disease process. It is therefore imperative that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson's. Drug repurposing has been recognized as being equally as promising as de novo drug discovery in the field of neurodegeneration and Parkinson's disease specifically...
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28399889/cardiac-pathology-in-spinal-muscular-atrophy-a-systematic-review
#3
REVIEW
C A Wijngaarde, A C Blank, M Stam, R I Wadman, L H van den Berg, W L van der Pol
BACKGROUND: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models...
April 11, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28378501/acl-reconstruction-does-not-induce-further-gamma-loop-abnormalities-on-the-intact-side-of-the-qf-a-longitudinal-study
#4
Yu Konishi
This study aimed to investigate the effect of surgery on the gamma-loop of the quadriceps on the side with an intact knee in patients with ACL injuries. We compared longitudinally the response of alpha motor neurons to vibration stimulation of the quadriceps on the side with an intact knee before and after ACL reconstruction. To evaluate alpha motor neuron response, we measured the maximal knee extension strength and integrated electromyography of the vastus medialis, vastus lateralis, and rectus femoris. After obtaining pre-vibration data from each subject, vibration stimulation was applied to the infrapatellar tendon, and the same measurements were performed immediately after stimulation...
April 4, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28370471/motor-deficits-and-beta-oscillations-are-dissociable-in-an-alpha-synuclein-model-of-parkinson-s-disease
#5
Ivani Brys, Jessica Nunes, Romulo Fuentes
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor symptoms resulting from chronic loss of dopaminergic neurons in the nigrostriatal pathway. The over expression of the protein alpha-synuclein in the substantia nigra has been used to induce progressive dopaminergic neuronal loss and to reproduce key histopathological and temporal features of PD in animal models. However the neurophysiological aspects of the alpha-synuclein PD model have been poorly characterized. Hereby we performed chronic in vivo electrophysiological recordings in the corticostriatal circuit of rats injected with viral vector to over express alpha-synuclein in the right substantia nigra...
March 30, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28362802/comparison-of-independent-screens-on-differentially-vulnerable-motor-neurons-reveals-alpha-synuclein-as-a-common-modifier-in-motor-neuron-diseases
#6
Rachel A Kline, Kevin A Kaifer, Erkan Y Osman, Francesco Carella, Ariana Tiberi, Jolill Ross, Giuseppa Pennetta, Christian L Lorson, Lyndsay M Murray
The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28336814/airway-smooth-muscle-dysfunction-in-pompe-gaa-mice
#7
Allison M Keeler, Donghai Liu, Marina Zieger, Lang Xiong, Jeffrey Salemi, Karl Bellve, Barry J Byrne, David D Fuller, Ronghua ZhuGe, Mai K ElMallah
Pompe disease is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA) - an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi, and this lower airway pathology contributes to respiratory insufficiency in Pompe disease...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28331094/herpes-simplex-virus-ge-gi-and-us9-promote-both-envelopment-and-sorting-of-virus-particles-in-the-cytoplasm-of-neurons-two-processes-that-precede-anterograde-transport-in-axons
#8
Grayson DuRaine, Todd W Wisner, Paul Howard, David C Johnson
Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently-infected ganglia to epithelial tissues where viral progeny are produced in numbers allowing spread to other hosts. HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. Previously we described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28326439/a-distinct-functional-distribution-of-%C3%AE-and-%C3%AE-motoneurons-in-the-rat-trigeminal-motor-nucleus
#9
Yukako Morita-Isogai, Hajime Sato, Mitsuru Saito, Eriko Kuramoto, Dong Xu Yin, Takeshi Kaneko, Takashi Yamashiro, Kenji Takada, Seog Bae Oh, Hiroki Toyoda, Youngnam Kang
Gamma-motoneurons (γMNs) play a crucial role in regulating isometric muscle contraction. The slow jaw-closing during mastication is one of the most functional isometric contractions, which is developed by the rank-order recruitment of alpha-motoneurons (αMNs) in a manner that reflects the size distribution of αMNs. In a mouse spinal motor nucleus, there are two populations of small and large MNs; the former was identified as a population of γMNs based on the positive expression of the transcription factor estrogen-related receptor 3 (Err3) and negative expression of the neuronal DNA-binding protein NeuN, and the latter as that of αMNs based on the opposite pattern of immunoreactivity...
March 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#10
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28278160/hyperleptinemia-in-children-with-autosomal-recessive-spinal-muscular-atrophy-type-i-iii
#11
Heike Kölbel, Berthold P Hauffa, Stefan A Wudy, Anastasios Bouikidis, Adela Della Marina, Ulrike Schara
BACKGROUND: Autosomal-recessive proximal spinal muscular atrophies (SMA) are disorders characterized by a ubiquitous deficiency of the survival of motor neuron protein that leads to a multisystemic disorder, which mostly affects alpha motor neurons. Disease progression is clinically associated with failure to thrive or weight loss, mainly caused by chewing and swallowing difficulties. Although pancreatic involvement has been described in animal models, systematic endocrinological evaluation of the energy metabolism in humans is lacking...
2017: PloS One
https://www.readbyqxmd.com/read/28270048/influence-of-transcutaneous-electrical-nerve-stimulation-conditions-on-disynaptic-reciprocal-ia-inhibition-and-presynaptic-inhibition-in-healthy-adults
#12
Kazuya Takeda, Shigeo Tanabe, Soichiro Koyama, Kosuke Ushiroyama, Yuki Naoi, Ikuo Motoya, Hiroaki Sakurai, Yoshikiyo Kanada
This study investigated the influence of stimulus conditions of transcutaneous electrical nerve stimulation (TENS) on disynaptic reciprocal Ia inhibition (RI) and presynaptic inhibition (D1 inhibition) in healthy adults. Eight healthy participants received TENS (stimulus frequencies of 50, 100, and 200 Hz) over the deep peroneal nerve and tibialis anterior (TA) muscle in the resting condition for 30 min. At pre- and post-intervention, the RI from the TA to the soleus (SOL) and D1 inhibition of the SOL alpha motor neuron were assessed by evoked electromyography...
March 2017: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/28267578/continuous-membrane-potential-fluctuations-in-motor-cortex-and-striatum-neurons-during-voluntary-forelimb-movements-and-pauses
#13
Satoshi Nonomura, Yoko Fujiwara-Tsukamoto, Takafumi Kajihara, Fumino Fujiyama, Yoshikazu Isomura
Theoretical simulations suggest that spike rate is regulated by varying both membrane potential and its fluctuation. We investigated whether membrane potential fluctuation functionally changes in motor cortex and striatum neurons during discrete forelimb movements and pauses, or at rest, using whole-cell recording in task-performing rats. Membrane potential fluctuation was diminished by task performance, but maintained overall in the alpha/beta and gamma bands during forelimb movements and pauses. By contrast, membrane potential itself was correlated with spike rate in task-related neurons...
March 4, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28259991/the-involvement-of-eag1-potassium-channels-and-mir-34a-in-rotenone-induced-death-of-dopaminergic-sh-sy5y-cells
#14
Camila Hillesheim Horst, Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
The loss of dopaminergic neurons and the resultant motor impairment are hallmarks of Parkinson's disease. The SH‑SY5Y cell line is a model of dopaminergic neurons, and allows for the study of dopaminergic neuronal injury. Previous studies have revealed changes in Ether à go‑go 1 (Eag1) potassium channel expression during p53-induced SH‑SY5Y apoptosis, and the regulatory involvement of microRNA‑34a (miR‑34a) was demonstrated. In the present study, the involvement of Eag1 and miR‑34a in rotenone‑induced SH‑SY5Y cell injury was investigated...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28229085/folate-receptor-alpha-is-more-than-just-a-folate-transporter
#15
Vineet Mohanty, M Rizwan Siddiqui, Tadanori Tomita, Chandra Shekhar Mayanil
Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. These observations beg a question: "Can a simple molecule such as folate be used to manipulate the production and/or differentiation of endogenous neural stem cells (NSCs), which may hold promise for future therapies?" Conditions such as spinal cord injury, motor neuron diseases, Alzheimer's disease and multiple sclerosis may benefit from increasing stem cell pool and promoting specific pathways of differentiation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28228579/network-wide-oscillations-in-the-parkinsonian-state-alterations-in-neuronal-activities-occur-in-the-premotor-cortex-in-parkinsonian-non-human-primates
#16
Jing Wang, Luke A Johnson, Alicia L Jensen, Kenneth B Baker, Jerrold L Vitek
A number of studies suggest that Parkinson's disease (PD) is associated with alterations of neuronal activity patterns in the basal-ganglia-thalamocortical circuit. There are limited electrophysiological data, however, describing how premotor cortex, which is involved in movement and decision making, is likely impacted in PD. In this study, spontaneous local field potential (LFP) and single unit neuronal activity were recorded in the dorsal premotor area of non-human primates in both the naïve and parkinsonian state using the MPTP model of parkinsonism...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28222554/a-single-group-pretest-posttest-clinical-trial-for-the-effects-of-dry-needling-on-wrist-flexors-spasticity-after-stroke
#17
Noureddin Nakhostin Ansari
BACKGROUND: Spasticity is a common complication after stroke. Dry needling (DN) is suggested as a novel method for treatment of muscle spasticity. OBJECTIVE: To explore the effects of DN on wrist flexors spasticity poststroke. METHODS: A single group, pretest-posttest clinical trial was used. Twenty nine patients with stroke (16 male; mean age 54.3 years) were tested at baseline (T0), immediately after DN (T1), and one hour after DN (T2). DN was applied for flexor carpi radialis (FCR) and flexor carpi ulnaris on the affected arm for single session, one minute per muscle...
February 8, 2017: NeuroRehabilitation
https://www.readbyqxmd.com/read/28192611/deficiency-of-trek-1-potassium-channel-exacerbates-secondary-injury-following-spinal-cord-injury-in-mice
#18
Yongkang Fang, Xiaojiang Huang, Yue Wan, Hao Tian, Yeye Tian, Wei Wang, Suiqiang Zhu, Minjie Xie
Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI...
February 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28095363/curcumin-confers-neuroprotection-against-alcohol-induced-hippocampal-neurodegeneration-via-creb-bdnf-pathway-in-rats
#19
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Hajar Hashemi, Mina Gholami
BACKGROUND: Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. METHODS: Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28062370/treadmill-exercise-alleviates-motor-deficits-and-improves-mitochondrial-import-machinery-in-an-mptp-induced-mouse-model-of-parkinson-s-disease
#20
Jung-Hoon Koo, Joon-Yong Cho, Ung-Bae Lee
Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression...
January 4, 2017: Experimental Gerontology
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