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https://www.readbyqxmd.com/read/29323043/neural-computational-modeling-reveals-a-major-role-of-corticospinal-gating-of-central-oscillations-in-the-generation-of-essential-tremor
#1
Hong-En Qu, Chuanxin M Niu, Si Li, Man-Zhao Hao, Zi-Xiang Hu, Qing Xie, Ning Lan
Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29299640/variable-impact-of-tizanidine-on-the-medium-latency-reflex-of-upper-and-lower-limbs
#2
Isaac Kurtzer, Laurent J Bouyer, J Bouffard, A Jin, L Christiansen, J B Nielsen, S H Scott
Sudden limb displacement evokes a complex sequence of compensatory muscle activity. Following the short-latency reflex and preceding voluntary reactions is an epoch termed the medium-latency reflex (MLR) that could reflect spinal processing of group II muscle afferents. One way to test this possibility is oral ingestion of tizanidine, an alpha-2 adrenergic agonist that inhibits the interneurons transmitting group II signals onto spinal motor neurons. We examined whether group II afferents contribute to MLR activity throughout the major muscles that span the elbow and shoulder...
January 3, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/29278715/accumulation-of-beta-synuclein-in-cortical-neurons-is-associated-with-autophagy-attenuation-in-the-brains-of-dementia-with-lewy-body-patients
#3
Tracey Evans, Wai Ling Kok, Katrina Cowan, Megan Hefford, Oleg Anichtchik
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls...
December 23, 2017: Brain Research
https://www.readbyqxmd.com/read/29249806/cortical-high-gamma-network-oscillations-and-connectivity-a-translational-index-for-antipsychotics-to-normalize-aberrant-neurophysiological-activity
#4
A Ahnaou, H Huysmans, T Van de Casteele, W H I M Drinkenburg
Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801)...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29229552/caspase-6-is-a-dispensable-enabler-of-adult-mammalian-axonal-degeneration
#5
V Woo, C Cheng, A Duraikannu, A Chandrasekhar, K Purdy, J A Martinez, D W Zochodne
The progress of axonal degeneration (AxD) following injury or insult impacts both recovery from axonal transection and protection of axons from diverse insults, or axonopathy. Here we provide evidence that increases in capase-6 (Casp6) expression and action contribute to the progression of AxD. The expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing AxD was confirmed. We developed and utilized a new model of axonopathy in live mice by serially visualizing the viability of cutaneous axons in the ear pinna that expressed an axonal YFP transgene, in response to capasaicin-induced AxD...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29218419/an-unexpected-improvement-in-spatial-learning-and-memory-ability-in-alpha-synuclein-a53t-transgenic-mice
#6
Qi Liu, YuYu Xu, WenPing Wan, ZeGang Ma
Growing evidence suggests, as Parkinson's disease (PD) progresses, that its non-motor symptoms appear prior to or in parallel with its motor deficits. Alpha-synuclein A53T transgenic mouse (A53T) is an essential tool to investigate the onsets and the extents of PD non-motor symptoms. Our aim is to investigate spatial learning and memory ability in A53T mice. In our rotarod tests, no motor coordination impairments were detected in mice of 3, 6, 9, and 12 months old. We then investigated their spatial learning and memory ability through Morris water maze in 3- and 9-month-old mice...
December 7, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29217155/pleiotropic-neuropathological-and-biochemical-alterations-associated-with-myo5a-mutation-in-a-rat-model
#7
Kerstin K Landrock, Patti Sullivan, Heidi Martini-Stoica, David S Goldstein, Brett H Graham, Shinya Yamamoto, Hugo J Bellen, Richard A Gibbs, Rui Chen, Marcello D'Amelio, George Stoica
In this study, we analyze the neuropathological and biochemical alterations involved in the pathogenesis of a neurodegenerative/movement disorder during different developmental stages in juvenile rats with a mutant Myosin5a (Myo5a). In mutant rats, a spontaneous autosomal recessive mutation characterized by the absence of Myo5a protein expression in the brain is associated with a syndrome of locomotor dysfunction, altered coat color, and neuroendocrine abnormalities. Myo5a encodes a myosin motor protein required for transport and proper distribution of subcellular organelles in somatodendritic processes in neurons...
December 4, 2017: Brain Research
https://www.readbyqxmd.com/read/29215752/familial-tauopathy-with-p364s-mapt-mutation-clinical-course-neuropathology-and-ultrastructure-of-neuronal-tau-inclusions
#8
Peter Štrafela, Jerica Pleško, Jožef Magdič, Blaž Koritnik, Andrej Zupan, Damjan Glavač, Mara Bresjanac, Mara Popović
AIMS: This report presents the clinical course, neuropathology and ultrastructure of neuronal tau inclusions of four Slovene relatives with P364S MAPT mutation. METHODS: The clinical history of three out of four P364S MAPT mutation carriers was taken. After formalin fixation, thorough sampling of the central nervous system was followed by paraffin embedding, H&E, Gallyas, Bielschowsky, and immunostaining with AT8, anti-3R, anti-4R tau, anti-Amyloid-β, anti-TDP43, and anti-alpha-synuclein antibodies...
December 7, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29184069/phosphorylated-exogenous-alpha-synuclein-fibrils-exacerbate-pathology-and-induce-neuronal-dysfunction-in-mice
#9
Mantia Karampetsou, Mustafa T Ardah, Maria Semitekolou, Alexia Polissidis, Martina Samiotaki, Maria Kalomoiri, Nour Majbour, Georgina Xanthou, Omar M A El-Agnaf, Kostas Vekrellis
Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at serine 129 suggesting that the accumulation of phosphorylated α-Synuclein is critical in the pathogenesis of Parkinson's disease. However, in vivo experiments addressing the role of phosphorylated α-Synuclein in the progression of Parkinson's disease have produced equivocal data. To clarify a role of Ser129 phosphorylation of α-Synuclein in pathology progression we performed stereotaxic injections targeting the mouse striatum with three fibrilar α-Synuclein types: wt-fibrils, phosphorylated S129 fibrils and, phosphorylation incompetent, S129A fibrils...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180135/alpha-synuclein-transgenic-mice-h-%C3%AE-synl62-display-%C3%AE-syn-aggregation-and-a-dopaminergic-phenotype-reminiscent-of-parkinson-s-disease
#10
Silke Frahm, Valeria Melis, David Horsley, Janet E Rickard, Gernot Riedel, Paula Fadda, Maria Scherma, Charles R Harrington, Claude M Wischik, Franz Theuring, Karima Schwab
Alpha-Synuclein (α-Syn) accumulation is considered a major risk factor for the development of synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies. We have generated mice overexpressing full-length human α-Syn fused to a membrane-targeting signal sequence under the control of the mouse Thy1-promotor. Three separate lines (L56, L58 and L62) with similar gene expression levels, but considerably heightened protein accumulation in L58 and L62, were established. In L62, there was widespread labelling of α-Syn immunoreactivity in brain including spinal cord, basal forebrain, cortex and striatum...
February 26, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29140156/conditioned-medium-from-human-gingival-mesenchymal-stem-cells-protects-motor-neuron-like-nsc-34-cells-against-scratch-injury-induced-cell-death
#11
Thangavelu Soundara Rajan, Francesca Diomede, Placido Bramanti, Oriana Trubiani, Emanuela Mazzon
Neuronal cell death is a normal process during central nervous system (CNS) development and is also involved in the death of motor neurons in diverse spinal motor neuron degenerative diseases. Here, we investigated the neuroprotective effect of secretory factors released from human gingival mesenchymal stem cells (hGMSCs) in mechanically injured murine motor-neuron-like NSC-34 cells. The cells were exposed to scratch injury and the markers for apoptosis and oxidative stress were examined. Immunocytochemistry results showed that proapoptotic markers cleaved caspase-3 and Bax were elevated while anti-apoptotic protein Bcl-2 was suppressed in scratch-injured NSC-34 cells...
November 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29128679/early-onset-epileptic-encephalopathy-with-de-novo-scn8a-mutation
#12
Yangyang Xiao, Jie Xiong, Ding'an Mao, Lingjuan Liu, Jian Li, Xingfang Li, Haiyan Luo, Liqun Liu
Early-onset epileptic encephalopathies (EOEEs) are clinically and genetically heterogeneous disorders characterized by intractable seizures and unremitting interictal paroxysmal epileptiform activity. Consequently, these syndromes impair neurodevelopment during the first year of life. Currently, the etiology of these disorders is largely unknown. In this study, Childhood-Onset Epilepsy Gene Panel Testing (containing 511 epilepsy-related genes) was performed in a parent-offspring trio. In this family, the son had refractory seizures, intellectual disability, and motor abnormalities, and he was diagnosed with EOEE...
October 28, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29063640/amyotrophic-lateral-sclerosis-and-parkinsonism-dementia-complex-of-the-hohara-focus-of-the-kii-peninsula-a-multiple-proteinopathy
#13
REVIEW
Maya Mimuro, Mari Yoshida, Shigeki Kuzuhara, Yasumasa Kokubo
The high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) has been previously known in the Kii Peninsula of Japan and in Guam. Recently, the accumulation of various proteins, such as tau, trans-activation response DNA binding protein 43 kDa (TDP-43), and alpha-synuclein (αSyn), was reported in the brains of patients with ALS/PDC in Guam. To confirm whether similar findings are present in Kii ALS/PDC, we neuropathologically examined the brains and spinal cords of 18 patients with ALS/PDC (clinical diagnoses: eight ALS and 10 PDC) in Hohara Village, which is the eastern focus of Kii ALS...
October 23, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29054880/common-synaptic-input-to-motor-neurons-and-neural-drive-to-targeted-reinnervated-muscles
#14
D Farina, A M Castronovo, I Vujaklija, A Sturma, S Salminger, C Hofer, O C Aszmann
We compared the behaviour of motor neurons innervating their physiological muscle targets with motor neurons from the same spinal segment whose axons were surgically redirected to remnant muscles (targeted muscle reinnervation). The objective was to assess whether motor neurons with non-physiological innervation receive similar synaptic input and could be voluntary controlled as motor neurons with natural innervation. For this purpose, we acquired high-density EMG signals from the biceps brachii in 5 male trans-humeral amputees who underwent targeted reinnervation of this muscle by the ulnar nerve and from the first dorsal interosseous muscle of 5 healthy individuals to investigate the natural innervation of the ulnar nerve...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29030055/the-heart-of-pd-lewy-body-diseases-as-neurocardiologic-disorders
#15
David S Goldstein, Yehonatan Sharabi
This review provides an update about cardiac sympathetic denervation in Lewy body diseases. The family of Lewy body diseases includes Parkinson's disease (PD), pure autonomic failure (PAF), and dementia with Lewy bodies (DLB). All three feature intra-neuronal cytoplasmic deposits of the protein, alpha-synuclein. Multiple system atrophy (MSA), the parkinsonian form of which can be difficult to distinguish from PD with orthostatic hypotension, involves glial cytoplasmic inclusions that contain alpha-synuclein...
October 10, 2017: Brain Research
https://www.readbyqxmd.com/read/29021741/the-neuroprotective-role-of-protein-quality-control-in-halting-the-development-of-alpha-synuclein-pathology
#16
REVIEW
Destiny-Love Manecka, Benoît Vanderperre, Edward A Fon, Thomas M Durcan
Synucleinopathies are a family of neurodegenerative disorders that comprises Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Each of these disorders is characterized by devastating motor, cognitive, and autonomic consequences. Current treatments for synucleinopathies are not curative and are limited to improvement of quality of life for affected individuals. Although the underlying causes of these diseases are unknown, a shared pathological hallmark is the presence of proteinaceous inclusions containing the α-synuclein (α-syn) protein in brain tissue...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29019159/alpha-lipoamide-ameliorates-motor-deficits-and-mitochondrial-dynamics-in-the-parkinson-s-disease-model-induced-by-6-hydroxydopamine
#17
Bo Zhou, Min Wen, Xin Lin, Yun-Hua Chen, Yun Gou, Yong Li, Yi Zhang, Hong-Wei Li, Lei Tang
The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are not yet fully elucidated; however, evidence from the in vitro and in vivo PD models suggest that mitochondrial dysfunction may play a major role in PD pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is a better cofactor for mitochondrial dehydrogenase with a stronger protective effect on mitochondria than lipoic acid. Identification of these protective effects of alpha lipoamide on mitochondria, together with the evidence that mitochondrial dysfunction plays a critical role in PD, we speculate that alpha lipoamide may exert a protective effect in PD by regulating the mitochondrial function...
October 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28986235/alpha-synuclein-epigenetics-mitochondria-metabolism-calcium-traffic-circadian-dysfunction-in-parkinson-s-disease-an-integrated-strategy-for-management
#18
REVIEW
Oliver T Phillipson
The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features...
November 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28924920/age-dependent-alpha-synuclein-accumulation-and-phosphorylation-in-the-enteric-nervous-system-in-a-transgenic-mouse-model-of-parkinson-s-disease
#19
Chong-Bin Zhong, Qian-Qian Chen, Caroline Haikal, Wen Li, Alexander Svanbergsson, Meike Diepenbroek, Jia-Yi Li
The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model...
October 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28923922/trkb-neurotrophic-activities-are-blocked-by-%C3%AE-synuclein-triggering-dopaminergic-cell-death-in-parkinson-s-disease
#20
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Matthew J Benskey, Xuebing Cao, Jun Xu, Yi E Sun, Keqiang Ye
BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson's disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
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