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https://www.readbyqxmd.com/read/28676095/toll-like-receptor-4-stimulation-with-monophosphoryl-lipid-a-ameliorates-motor-deficits-and-nigral-neurodegeneration-triggered-by-extraneuronal-%C3%AE-synucleinopathy
#1
Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K Wenning, Nadia Stefanova
BACKGROUND: Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be a natural mechanism to improve the clearance of α-syn...
July 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28659169/the-novel-compound-pbt434-prevents-iron-mediated-neurodegeneration-and-alpha-synuclein-toxicity-in-multiple-models-of-parkinson-s-disease
#2
David I Finkelstein, Jessica L Billings, Paul A Adlard, Scott Ayton, Amelia Sedjahtera, Colin L Masters, Simon Wilkins, David M Shackleford, Susan A Charman, Wojciech Bal, Izabela A Zawisza, Ewa Kurowska, Andrew L Gundlach, Sheri Ma, Ashley I Bush, Dominic J Hare, Philip A Doble, Simon Crawford, Elisabeth Cl Gautier, Jack Parsons, Penny Huggins, Kevin J Barnham, Robert A Cherny
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions...
June 28, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28656548/treadmill-exercise-attenuates-%C3%AE-synuclein-levels-by-promoting-mitochondrial-function-and-autophagy-possibly-via-sirt1-in-the-chronic-mptp-p-induced-mouse-model-of-parkinson-s-disease
#3
Jung-Hoon Koo, Joon-Yong Cho
Accumulation of alpha-synuclein (α-Syn) is significantly correlated with the presence of progressive motor deficits, which is the main symptom of Parkinson's disease (PD). Although physical exercise reduces α-Syn levels, the molecular mechanisms by which physical exercise decreases α-Syn remain unclear. We hypothesized that treadmill exercise (TE) decreases α-Syn levels by improving mitochondrial function and promoting autophagy via the sirtuin-1 (SIRT1) signaling pathway in the chronic 1-methyl-1,2,3,6-tetrahydropyridine with probenecid (MPTP/P)-induced mouse model of PD...
June 27, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28651628/separability-of-motor-imagery-of-the-self-from-interpretation-of-motor-intentions-of-others-at-the-single-trial-level-an-eeg-study
#4
João Andrade, José Cecílio, Marco Simões, Francisco Sales, Miguel Castelo-Branco
BACKGROUND: We aimed to investigate the separability of the neural correlates of 2 types of motor imagery, self and third person (actions owned by the participant himself vs. another individual). If possible this would allow for the development of BCI interfaces to train disorders of action and intention understanding beyond simple imitation, such as autism. METHODS: We used EEG recordings from 20 healthy participants, as well as electrocorticography (ECoG) in one, based on a virtual reality setup...
June 26, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28645308/neonatal-aav-delivery-of-alpha-synuclein-induces-pathology-in-the-adult-mouse-brain
#5
Marion Delenclos, Ayman H Faroqi, Mei Yue, Aishe Kurti, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, John D Fryer, Pamela J McLean
Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28635376/advances-in-understanding-the-role-of-disease-associated-proteins-in-spinal-muscular-atrophy
#6
Seyyedmohsen Hosseinibarkooie, Svenja Schneider, Brunhilde Wirth
Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by alpha motor neuron loss in the spinal cord due to reduced survival motor neuron (SMN) protein level. While the genetic basis of SMA is well described, the specific molecular pathway underlying SMA is still not fully understood. Areas covered: This review discusses the recent advancements in understanding the molecular pathways in SMA using different omics approaches and genetic modifiers identified in both vertebrate and invertebrate systems...
June 30, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28611575/ica-derived-eeg-correlates-to-mental-fatigue-effort-and-workload-in-a-realistically-simulated-air-traffic-control-task
#7
Deepika Dasari, Guofa Shou, Lei Ding
Electroencephalograph (EEG) has been increasingly studied to identify distinct mental factors when persons perform cognitively demanding tasks. However, most of these studies examined EEG correlates at channel domain, which suffers the limitation that EEG signals are the mixture of multiple underlying neuronal sources due to the volume conduction effect. Moreover, few studies have been conducted in real-world tasks. To precisely probe EEG correlates with specific neural substrates to mental factors in real-world tasks, the present study examined EEG correlates to three mental factors, i...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28585189/modulatory-role-of-nurr1-activation-and-thrombin-inhibition-in-the-neuroprotective-effects-of-dabigatran-etexilate-in-rotenone-induced-parkinson-s-disease-in-rats
#8
Esraa A Kandil, Rabab H Sayed, Lamiaa A Ahmed, Mai A Abd El Fattah, Bahia M El-Sayeh
Recently, it has been shown that both decreased nuclear receptor-related 1 (Nurr1) expression and thrombin accumulation are involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). The new anticoagulant dabigatran etexilate (DE) is a direct thrombin inhibitor that owns benzimidazole group, which has been proposed to activate Nurr1. In the present study, we examined the neuroprotective effects of DE in rotenone model of PD. Rotenone was injected subcutaneously at a dose of 1.5 mg/kg every other day for 21 days...
June 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28566250/local-somatodendritic-translation-and-hyperphosphorylation-of-tau-protein-triggered-by-ampa-and-nmda-receptor-stimulation
#9
Shunsuke Kobayashi, Toru Tanaka, Yoshiyuki Soeda, Osborne F X Almeida, Akihiko Takashima
Tau is a major component of the neurofibrillary tangles (NFT) that represent a pathological hallmark of Alzheimer's disease (AD). Although generally considered an axonal protein, Tau is found in the somato-dendritic compartment of degenerating neurons and this redistribution is thought to be a trigger of neurodegeneration in AD. Here, we show the presence of tau mRNA in a dendritic ribonucleoprotein (RNP) complex that includes Ca2(+)-calmodulin dependent protein kinase (CaMK)IIα mRNA and that is translated locally in response to glutamate stimulation...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28559380/crossmodal-classification-of-mu-rhythm-activity-during-action-observation-and-execution-suggests-specificity-to-somatosensory-features-of-actions
#10
Michel-Pierre Coll, Clare Press, Hannah Hobson, Caroline Catmur, Geoffrey Bird
The alpha mu rhythm (8-13 Hz) has been considered to reflect mirror neuron activity because it is attenuated by both action observation and action execution. The putative link between mirror neuron system activity and the mu rhythm has been used to study the involvement of the mirror system in a wide range of socio-cognitive processes and clinical disorders. However, previous research has failed to convincingly demonstrate the specificity of the mu rhythm, meaning that it is unclear whether the mu rhythm reflects mirror neuron activity...
June 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28556404/viral-mediated-oligodendroglial-alpha-synuclein-expression-models-multiple-system-atrophy
#11
Fares Bassil, Paul A Guerin, Nathalie Dutheil, Qin Li, Matthias Klugmann, Wassilios G Meissner, Erwan Bezard, Pierre-Olivier Fernagut
BACKGROUND: MSA is a fatal neurodegenerative disorder characterized by a combination of autonomic dysfunction, cerebellar ataxia, and l-dopa unresponsive parkinsonism. The hallmark of MSA is the accumulation of α-synuclein, forming cytoplasmic inclusions in oligodendrocytes. Adeno-associated viruses allow efficient targeting of disease-associated genes in selected cellular ensembles and have proven efficient for the neuronal overexpression of α-synuclein in the substantia nigra in the context of PD...
May 29, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28555126/altered-motor-unit-discharge-coherence-in-paretic-muscles-of-stroke-survivors
#12
Chenyun Dai, Nina L Suresh, Aneesha K Suresh, William Zev Rymer, Xiaogang Hu
After a cerebral stroke, a series of changes at the supraspinal and spinal nervous system can alter the control of muscle activation, leading to persistent motor impairment. However, the relative contribution of these different levels of the nervous system to impaired muscle activation is not well understood. The coherence of motor unit (MU) spike trains is considered to partly reflect activities of higher level control, with different frequency band representing different levels of control. Accordingly, the objective of this study was to quantify the different sources of contribution to altered muscle activation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28549787/the-gut-brain-axis-in-parkinson-s-disease-possibilities-for-food-based-therapies
#13
Paula Perez-Pardo, Tessa Kliest, Hemraj B Dodiya, Laus M Broersen, Johan Garssen, Ali Keshavarzian, Aletta D Kraneveld
Parkinson's disease (PD) is usually characterized by cardinal motor impairments. However, a range of non-motor symptoms precede the motor-phase and are major determinants for the quality of life. To date, no disease modifying treatment is available for PD patients. The gold standard therapy of levodopa is based on restoring dopaminergic neurotransmission, thereby alleviating motor symptoms, whereas non-motor symptoms remain undertreated. One of the most common non-motor symptoms is gastrointestinal dysfunction usually associated with alpha-synuclein accumulations and low-grade mucosal inflammation in the enteric nervous system...
May 23, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28545543/inhibition-of-colony-stimulating-factor-1-receptor-early-in-disease-ameliorates-motor-deficits-in-sca1-mice
#14
Wenhui Qu, Andrea Johnson, Joo Hyun Kim, Abigail Lukowicz, Daniel Svedberg, Marija Cvetanovic
BACKGROUND: Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1...
May 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28536546/only-three-fingers-write-but-the-whole-brain-works-a-high-density-eeg-study-showing-advantages-of-drawing-over-typing-for-learning
#15
Audrey L H van der Meer, F R Ruud van der Weel
Are different parts of the brain active when we type on a keyboard as opposed to when we draw visual images on a tablet? Electroencephalogram (EEG) was used in young adults to study brain electrical activity as they were typing or describing in words visually presented Pictionary(TM) words using a keyboard, or as they were drawing pictures of the same words on a tablet using a stylus. Analyses of temporal spectral evolution (time-dependent amplitude changes) were performed on EEG data recorded with a 256-channel sensor array...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28522369/electroencephalographic-monitoring-during-sevoflurane-anaesthesia-in-an-amyotrophic-lateral-sclerosis-patient-with-locked-in-state
#16
Kazuko Hayashi, Ryuhei Araki, Akiko Tanaka
Recently, the cognitive abilities of patients with amyotrophic lateral sclerosis (ALS) have been found to be impaired along with the neurodegeneration of motor neurons. Electroencephalography (EEG) of end-stage ALS patients has reportedly shown specific features based on neuronal network modulations, differing from EEG of other patients with cognitive failure and dementia. However, EEG of end-stage ALS patients during anaesthesia has not yet been reported. A 64-year-old male ALS patient with locked-in state (LIS), supported by tracheostomy positive-pressure ventilation (TPPV) and enteral nourishment for 9years, underwent scheduled general anaesthesia for repair of a fractured mandible...
May 15, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#17
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28484373/evolution-and-development-of-the-inner-ear-efferent-system-transforming-a-motor-neuron-population-to-connect-to-the-most-unusual-motor-protein-via-ancient-nicotinic-receptors
#18
REVIEW
Bernd Fritzsch, Karen L Elliott
All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs). Comparative data suggest that IEEs derive from facial branchial motor (FBM) neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS), efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28483975/developmental-disruption-of-recurrent-inhibitory-feedback-results-in-compensatory-adaptation-in-the-renshaw-cell-motor-neuron-circuit
#19
Anders Enjin, Sharn Perry, Markus M Hilscher, Chetan Nagaraja, Martin Larhammar, Henrik Gezelius, Anders Eriksson, Katarina E Leão, Klas Kullander
When activating muscles, motor neurons in the spinal cord also activate Renshaw cells, which provide recurrent inhibitory feedback to the motor neurons. The tight coupling with motor neurons suggests that Renshaw cells have an integral role in movement, a role that is yet to be elucidated. Here we used the selective expression of the nicotinic cholinergic receptor alpha 2 (Chrna2) in mice to genetically target the vesicular inhibitory amino acid transporter (VIAAT) in Renshaw cells. Loss of VIAAT from Chrna2(Cre) expressing Renshaw cells did not impact any aspect of drug-induced fictive locomotion in the neonatal mouse, nor did it change gait, motor coordination or grip strength in adult mice of both sexes...
May 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28476511/training-of-support-afferentation-in-postmenopausal-women
#20
O M Bazanova, N V Kholodina, E D Nikolenko, J Payet
We have recently shown a diminishing of the Menopause Index in old-aged women who underwent special training directed at the enhancement of support afferentation by increasing the plantar forefoot sensitivity (Bazanova et al., 2015). Based on these results we hypothesized, that purposeful training of support afferentation through stimulation of plantar graviceptors by Aikido practice will decrease excessive postural and psychoemotional tension not only in rest condition, but during cognitive and manual task performance too...
May 2, 2017: International Journal of Psychophysiology
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