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https://www.readbyqxmd.com/read/28453791/progranulin-functions-as-a-cathepsin-d-chaperone-to-stimulate-axonal-outgrowth-in-vivo
#1
Sander Beel, Matthieu Moisse, Markus Damme, Louis De Muynck, Wim Robberecht, Ludo Van Den Bosch, Paul Saftig, Philip Van Damme
Loss of function mutations in progranulin (GRN) cause frontotemporal dementia, but how GRN haploinsufficiency causes neuronal dysfunction remains unclear. We previously showed that GRN is neurotrophic in vitro. Here, we used an in vivo axonal outgrowth system and observed a delayed recovery in GRN-/- mice after facial nerve injury. This deficit was rescued by reintroduction of human GRN and relied on its C-terminus and on neuronal GRN production. Transcriptome analysis of the facial motor nucleus post injury identified cathepsin D (CTSD) as the most upregulated gene...
April 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28453527/altered-nucleocytoplasmic-proteome-and-transcriptome-distributions-in-an-in-vitro-model-of-amyotrophic-lateral-sclerosis
#2
Jee-Eun Kim, Yoon Ho Hong, Jin Young Kim, Gye Sun Jeon, Jung Hee Jung, Byung-Nam Yoon, Sung-Yeon Son, Kwang-Woo Lee, Jong-Il Kim, Jung-Joon Sung
Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS...
2017: PloS One
https://www.readbyqxmd.com/read/28448548/altered-striatal-endocannabinoid-signaling-in-a-transgenic-mouse-model-of-spinocerebellar-ataxia-type-3
#3
Carmen Rodríguez-Cueto, Mariluz Hernández-Gálvez, Cecilia J Hillard, Patricia Maciel, Sara Valdeolivas, José A Ramos, María Gómez-Ruiz, Javier Fernández-Ruiz
Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice...
2017: PloS One
https://www.readbyqxmd.com/read/28448298/anesthetic-consideration-for-neuromuscular-diseases
#4
Jeffery A Katz, Glenn S Murphy
PURPOSE OF REVIEW: The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients...
April 26, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28448016/zebrafish-in-situ-spinal-cord-preparation-for-electrophysiological-recordings-from-spinal-sensory-and-motor-neurons
#5
Rosa L Moreno, Megan Josey, Angeles B Ribera
Zebrafish, first introduced as a developmental model, have gained popularity in many other fields. The ease of rearing large numbers of rapidly developing organisms, combined with the embryonic optical clarity, served as initial compelling attributes of this model. Over the past two decades, the success of this model has been further propelled by its amenability to large-scale mutagenesis screens and by the ease of transgenesis. More recently, gene-editing approaches have extended the power of the model. For neurodevelopmental studies, the zebrafish embryo and larva provide a model to which multiple methods can be applied...
April 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447571/neuroprotective-effects-of-betulin-in-pharmacological-and-transgenic-c-elegans-models-of-parkinson-s-disease
#6
Chia-Wen Tsai, Rong-Tzong Tsai, Shih-Ping Liu, Chang-Shi Chen, Min-Chen Tsai, Shao-Hsuan Chien, Huey-Shan Hung, Shinn-Zong Lin, Woei-Cherng Shyu, Ru-Huei Fu
Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly.It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Currently, therapeutics for PD provide satisfactory symptom relief, but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28446867/response-properties-of-motor-equivalence-neurons-of-the-primate-premotor-cortex
#7
Eleftherios Neromyliotis, A K Moschovakis
To study the response properties of cells that could participate in eye-hand coordination we trained two macaque monkeys to perform center-out saccades and pointing movements with their right or left forelimb toward visual targets presented on a video display. We analyzed the phasic movement related discharges of neurons of the periarcuate cortex that fire before and during saccades and movements of the hand whether accompanied by movements of the other effector or not. Because such cells could encode an abstract form of the desired displacement vector without regard to the effector that would execute the movement we refer to such cells as motor equivalence neurons (Meq)...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#8
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28446588/hierarchical-differences-in-population-coding-within-auditory-cortex
#9
Joshua David Downer, Mamiko Niwa, Mitchell L Sutter
Most models of auditory cortical (AC) population coding have focused on primary auditory cortex (A1). Thus, our understanding of how neural coding for sounds progresses along the cortical hierarchy remains obscure. To illuminate this, we recorded from AC fields, A1 and middle-lateral belt (ML) of rhesus macaques. We presented amplitude-modulated (AM) noise during both passive listening and while the animals performed an AM detection task ("Active" condition). In both fields, neurons exhibit monotonic AM-depth tuning, with A1 neurons mostly exhibiting increasing rate-depth functions and ML neurons ~evenly distributed between increasing and decreasing functions...
April 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#10
Goutam Chandra, Avik Roy, Suresh B Rangasamy, Kalipada Pahan
Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most widely used animal model for Parkinson's disease (PD), it is known that nigrostriatal pathologies do not persist in the acute MPTP mouse model. This study highlights the importance of adaptive immunity in driving persistent and progressive disease in acute MPTP-intoxicated mice. Although marked infiltration of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration decreased afterward, becoming normal on 30 d of insult...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446119/neurobionics-and-the-brain-computer-interface-current-applications-and-future-horizons
#11
Jeffrey V Rosenfeld, Yan Tat Wong
The brain-computer interface (BCI) is an exciting advance in neuroscience and engineering. In a motor BCI, electrical recordings from the motor cortex of paralysed humans are decoded by a computer and used to drive robotic arms or to restore movement in a paralysed hand by stimulating the muscles in the forearm. Simultaneously integrating a BCI with the sensory cortex will further enhance dexterity and fine control. BCIs are also being developed to: provide ambulation for paraplegic patients through controlling robotic exoskeletons; restore vision in people with acquired blindness; detect and control epileptic seizures; and improve control of movement disorders and memory enhancement...
May 1, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28446118/motor-neurone-disease-progress-and-challenges
#12
Thanuja Dharmadasa, Robert D Henderson, Paul S Talman, Richard Al Macdonell, Susan Mathers, David W Schultz, Merrillee Needham, Margaret Zoing, Steve Vucic, Matthew C Kiernan
Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals...
May 1, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#13
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445732/the-hect-family-ubiquitin-ligase-eel-1-regulates-neuronal-function-and-development
#14
Karla J Opperman, Ben Mulcahy, Andrew C Giles, Monica G Risley, Rayna L Birnbaum, Erik D Tulgren, Ken Dawson-Scully, Mei Zhen, Brock Grill
Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with intellectual disability, but it remains unknown whether HUWE1 functions in post-mitotic neurons to affect circuit function. Using genetics, pharmacology, and electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans, preferentially regulates GABAergic presynaptic transmission. Decreasing or increasing EEL-1 function alters GABAergic transmission and the excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to impaired locomotion and increased sensitivity to electroshock...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445715/altered-somatosensory-cortex-neuronal-activity-in-a-rat-model-of-parkinson-s-disease-and-levodopa-induced-dyskinesias
#15
Mesbah Alam, Regina Rumpel, Xingxing Jin, Christof von Wrangel, Sarah Tschirner, Joachim K Krauss, Claudia Grothe, Andreas Ratzka, Kerstin Schwabe
Several findings support the concept that sensorimotor integration is disturbed in Parkinson's disease (PD) and in levodopa-induced dyskinesias. In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under urethane (1...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28445613/neuronal-distribution-of-tyramine-and-the-tyramine-receptor-amtar1-in-the-honeybee-brain
#16
Markus Thamm, Christina Scholl, Tina Reim, Kornelia Grübel, Karin Möller, Wolfgang Rössler, Ricarda Scheiner
Tyramine is an important neurotransmitter, neuromodulator, and neurohormone in insects. In honeybees, it is assumed to have functions in modulating sensory responsiveness and controlling motor behavior. Tyramine can bind to two characterized receptors in honeybees, both of which are coupled to intracellular cAMP pathways. How tyramine acts on neuronal, cellular and circuit levels is unclear. We investigated the spatial brain expression of the tyramine receptor AmTAR1 using a specific antibody. This antibody detects a membrane protein of the expected molecular weight in Western blot analysis...
April 26, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28445364/n-acetylcysteine-prevents-retrograde-motor-neuron-death-after-neonatal-peripheral-nerve-injury
#17
Joseph Catapano, Jennifer Zhang, David Scholl, Cameron Chiang, Tessa Gordon, Gregory H Borschel
BACKGROUND: Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury...
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28444311/expression-of-als-ftd-linked-mutant-ccnf-in-zebrafish-leads-to-increased-cell-death-in-the-spinal-cord-and-an-aberrant-motor-phenotype
#18
Alison L Hogan, Emily K Don, Stephanie L Rayner, Albert Lee, Angela S Laird, Maxinne Watchon, Claire Winnick, Ingrid S Tarr, Marco Morsch, Jennifer A Fifita, Serene Gwee, Isabel Formella, Elinor Hortle, Kristy Yuan, Mark P Molloy, Kelly L Williams, Garth A Nicholson, Roger S Chung, Ian P Blair, Nicholas J Cole
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease characterised by the death of upper and lower motor neurons. Approximately 10% of cases have a known family history of ALS and disease-linked mutations in multiple genes have been identified. ALS-linked mutations in CCNF were recently reported, however the pathogenic mechanisms associated with these mutations are yet to be established. To investigate possible disease mechanisms, we developed in vitro and in vivo models based on an ALS-linked missense mutation in CCNF...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28443381/pharmacological-management-of-narcolepsy-with-and-without-cataplexy
#19
Ulf Kallweit, Claudio L Bassetti
Introduction Narcolepsy is an orphan neurological disease and presents with sleep- wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28443372/cord-blood-as-a-potential-therapeutic-for-amyotrophic-lateral-sclerosis
#20
Svitlana Garbuzova-Davis, Jared Ehrhart, Paul R Sanberg
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival. Areas covered: Composition and in vitro and in vivo differentiation of hUCB cells and the advantages of cord blood as a source of transplant cells are discussed...
April 26, 2017: Expert Opinion on Biological Therapy
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