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https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#1
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#2
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28065938/efficient-implementation-of-a-real-time-estimation-system-for-thalamocortical-hidden-parkinsonian-properties
#3
Shuangming Yang, Bin Deng, Jiang Wang, Huiyan Li, Chen Liu, Chris Fietkiewicz, Kenneth A Loparo
Real-time estimation of dynamical characteristics of thalamocortical cells, such as dynamics of ion channels and membrane potentials, is useful and essential in the study of the thalamus in Parkinsonian state. However, measuring the dynamical properties of ion channels is extremely challenging experimentally and even impossible in clinical applications. This paper presents and evaluates a real-time estimation system for thalamocortical hidden properties. For the sake of efficiency, we use a field programmable gate array for strictly hardware-based computation and algorithm optimization...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053151/optimized-temporal-pattern-of-brain-stimulation-designed-by-computational-evolution
#4
David T Brocker, Brandon D Swan, Rosa Q So, Dennis A Turner, Robert E Gross, Warren M Grill
Brain stimulation is a promising therapy for several neurological disorders, including Parkinson's disease. Stimulation parameters are selected empirically and are limited to the frequency and intensity of stimulation. We varied the temporal pattern of deep brain stimulation to ameliorate symptoms in a parkinsonian animal model and in humans with Parkinson's disease. We used model-based computational evolution to optimize the stimulation pattern. The optimized pattern produced symptom relief comparable to that from standard high-frequency stimulation (a constant rate of 130 or 185 Hz) and outperformed frequency-matched standard stimulation in a parkinsonian rat model and in patients...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28042095/reduced-noradrenergic-innervation-of-ventral-midbrain-dopaminergic-cell-groups-and-the-subthalamic-nucleus-in-mptp-treated-parkinsonian-monkeys
#5
Gunasingh Jeyaraj Masilamoni, Olivia Groover, Yoland Smith
There is anatomical and functional evidence that ventral midbrain dopaminergic (DA) cell groups and the subthalamic nucleus (STN) receive noradrenergic innervation in rodents, but much less is known about these interactions in primates. Degeneration of NE neurons in the locus coeruleus (LC) and related brainstem NE cell groups is a well-established pathological feature of Parkinson's disease (PD), but the development of such pathology in animal models of PD has been inconsistent across species and laboratories...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28039987/a-neural-mass-model-of-basal-ganglia-nuclei-simulates-pathological-beta-rhythm-in-parkinson-s-disease
#6
Fei Liu, Jiang Wang, Chen Liu, Huiyan Li, Bin Deng, Chris Fietkiewicz, Kenneth A Loparo
An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network...
December 2016: Chaos
https://www.readbyqxmd.com/read/28038867/parkinsonian-axial-signs-in-schizophrenia
#7
Francesca Morgante, Corrado Barbui, Michele Tinazzi
INTRODUCTION: We have recently demonstrated evidence of nigro-striatal denervation, disease progression and response to levodopa in a subgroup of patients with schizophrenia who developed parkinsonism. OBJECTIVE: In the present study, we investigated whether axial parkinsonian signs might be an early manifestation of parkinsonism in schizophrenia not necessarily related to chronic administration of antipsychotic drugs (AP) drugs. METHODS: From a baseline cohort of 299 schizophrenic patients who did not satisfy the diagnostic criteria for parkinsonism (presence of at least two of the following appendicular signs: bradykinesia, tremor, rigidity), we identified a group of patients who manifested two out of three axial parkinsonian signs (abnormality of trunk posture, hypomimia and short-step gait)...
December 23, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28035939/could-mao-b-inhibitor-withdrawal-rather-than-nilotinib-benefit-explain-the-dopamine-metabolite-increase-in-parkinsonian-study-subjects
#8
Michael A Schwarzschild
No abstract text is available yet for this article.
December 23, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28034996/a-fully-automated-atlas-based-approach-for-superior-cerebellar-peduncle-evaluation-in-progressive-supranuclear-palsy-phenotypes
#9
G Nicoletti, M E Caligiuri, A Cherubini, M Morelli, F Novellino, G Arabia, M Salsone, A Quattrone
BACKGROUND AND PURPOSE: The superior cerebellar peduncle is damaged in progressive supranuclear palsy. However, alterations differ between progressive supranuclear palsy with Richardson syndrome and progressive supranuclear palsy-parkinsonism. In this study, we propose an automated tool for superior cerebellar peduncle integrity assessment and test its performance in patients with progressive supranuclear palsy with Richardson syndrome, progressive supranuclear palsy-parkinsonism, Parkinson disease, and healthy controls...
December 29, 2016: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28031394/dose-dependent-progression-of-parkinsonism-in-manganese-exposed-welders
#10
Brad A Racette, Susan Searles Nielsen, Susan R Criswell, Lianne Sheppard, Noah Seixas, Mark N Warden, Harvey Checkoway
OBJECTIVE: To determine whether the parkinsonian phenotype prevalent in welders is progressive, and whether progression is related to degree of exposure to manganese (Mn)-containing welding fume. METHODS: This was a trade union-based longitudinal cohort study of 886 American welding-exposed workers with 1,492 examinations by a movement disorders specialist, including 398 workers with 606 follow-up examinations up to 9.9 years after baseline. We performed linear mixed model regression with cumulative Mn exposure as the independent variable and annual change in Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) as the primary outcome, and subcategories of the UPDRS3 as secondary outcomes...
December 28, 2016: Neurology
https://www.readbyqxmd.com/read/28024573/l-dopa-co-drugs-in-nanostructured-lipid-carriers-a-comparative-study
#11
Rita Cortesi, Elisabetta Esposito, Markus Drechsler, Gabriella Pavoni, Ivana Cacciatore, Maddalena Sguizzato, Antonio Di Stefano
This paper describes the production and characterization of nanostructured lipid carriers (NLC) containing four different levodopa (LD) co-drugs (PD), named PDA (3,4-diacetyloxy-LD-caffeic acid co-drug), PDB (lipoic acid-dopamine co-drug), PDC (lipoic acid-3,4-diacetoxy-dopamine co-drug), and PDD (dimeric LD co-drug containing an alkyl linker), with therapeutic potential in Parkinson's disease. These co-drugs were produced with the aim of prolonging the pharmacological activity of LD, enhancing its absorption and protecting it from metabolism...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28018168/what-mechanisms-are-responsible-for-the-reuptake-of-levodopa-derived-dopamine-in-parkinsonian-striatum
#12
REVIEW
Haruo Nishijima, Masahiko Tomiyama
Levodopa is the most effective medication for motor symptoms in Parkinson's disease. However, various motor and non-motor complications are associated with levodopa treatment, resulting from altered levodopa-dopamine metabolism with disease progression and long-term use of the drug. The present review emphasizes the role of monoamine transporters other than the dopamine transporter in uptake of extracellular dopamine in the dopamine-denervated striatum. When dopaminergic neurons are lost and dopamine transporters decreased, serotonin and norepinephrine transporters compensate by increasing uptake of excessive extracellular dopamine in the striatum...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28017549/gender-effect-on-non-motor-symptoms-in-parkinson-s-disease-are-men-more-at-risk
#13
A Nicoletti, R Vasta, G Mostile, G Nicoletti, G Arabia, G Iliceto, P Lamberti, R Marconi, L Morgante, P Barone, A Quattrone, M Zappia
INTRODUCTION: Several gender differences have been reported in Parkinson's Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS: The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively...
December 13, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28017533/re-emergent-tremor-in-parkinson-s-disease-clinical-and-accelerometric-properties
#14
Zübeyde Aytürk, Rezzak Yilmaz, M Cenk Akbostanci
Re-emergent tremor (RET) and the classical parkinsonian rest tremor were considered as two different phenomena of the same central tremor circuit. However, clinical and accelerometric characteristics of these tremors were not previously compared in a single study. We evaluated disease characteristics and accelerometric measurements of two tremor types in 42 patients with Parkinson's disease. Disease specific features and accelerometric measurements of peak frequency, amplitude at peak frequency and the root mean square (RMS) amplitude of two tremor types were compared...
December 22, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28011385/the-effect-of-searsia-chirindensis-stem-bark-extract-on-renal-and-liver-function-in-a-rat-model-of-neurotoxicity
#15
Zulfiah Mohamed Moosa, Musa Mabandla
Searsia chirindensis (SC) (Baker F.) (Anacardiaceae) has shown potential for the treatment of many neurological diseases however its effect on other bodily systems in neurotoxic models is not well-documented. In this study we investigated the effects of SC on blood glucose homeostasis, as well as its effect on liver and kidney function by assessing lipid peroxidation using the TBARS assay and measuring plasma and urinary electrolyte concentrations in a 6-hydroxydopamine parkinsonian model. The relative levels of phytochemicals were also quantified, along with testing free radical scavenging activity via the DPPH assay...
December 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28009769/movement-disorders-induced-by-the-atypical-antipsychotic-aripiprazole
#16
Karim Selfani, Valérie L Soland, Sylvain Chouinard, Philippe Huot
OBJECTIVES: Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect...
January 2017: Neurologist
https://www.readbyqxmd.com/read/28008361/fuzzy-logic-based-risk-of-fall-estimation-using-smartwatch-data-as-a-means-to-form-an-assistive-feedback-mechanism-in-everyday-living-activities
#17
Dimitrios E Iakovakis, Fotini A Papadopoulou, Leontios J Hadjileontiadis
This Letter aims to create a fuzzy logic-based assistive prevention tool for falls, based on accessible sensory technology, such as smartwatch, resulting in monitoring of the risk factors of falls caused by orthostatic hypotension (OH); a drop in systolic blood pressure (DSBP) >20 mmHg due to postural changes. Epidemiological studies have shown that OH is a high risk factor for falls and has a strong impact in quality of life (QoL) of the elderly's, especially for some cases such as Parkinsonians. Based on smartwatch data, it is explored here how statistical features of heart rate variability (HRV) can lead to DSBP prediction and estimation of the risk of fall...
December 2016: Healthcare Technology Letters
https://www.readbyqxmd.com/read/28004201/autonomic-disturbances-including-impaired-hand-thermoregulation-in-multiple-system-atrophy-and-parkinson-s-disease
#18
Sarunas Augustis, Viktoras Saferis, Wolfgang H Jost
Autonomic dysfunction in multiple system atrophy (MSA) comprises cardinal symptoms of orthostatic hypotension (OH) and urinary incontinence. Additionally, cardiovagal and sudomotor abnormalities can be present. Previous studies compared hand skin temperature and its response to cooling in subjects with probable MSA and Parkinson's disease (PD). Significant differences were found indicating that disturbed thermoregulation belongs to MSA autonomic features and could be helpful in differentiation of MSA from PD...
December 21, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27999892/electromyographic-assessment-of-paratonia
#19
Lucio Marinelli, Laura Mori, Matteo Pardini, David Beversdorf, Leonardo Cocito, Antonio Currà, Francesco Fattapposta, Maria Felice Ghilardi, Giovanni Abbruzzese, Carlo Trompetto
Many years after its initial description, paratonia remains a poorly understood concept. It is described as the inability to relax muscles during muscle tone assessment with the subject involuntary facilitating or opposing the examiner. Although related to cognitive impairment and frontal lobe function, the underlying mechanisms have not been clarified. Moreover, criteria to distinguish oppositional paratonia from parkinsonian rigidity or spasticity are not yet available. Paratonia is very frequently encountered in clinical practice and only semi-quantitative rating scales are available...
December 20, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/27995072/application-of-texture-analysis-to-dat-spect-imaging-relationship-to-clinical-assessments
#20
Arman Rahmim, Yousef Salimpour, Saurabh Jain, Stephan A L Blinder, Ivan S Klyuzhin, Gwenn S Smith, Zoltan Mari, Vesna Sossi
Dopamine transporter (DAT) SPECT imaging is increasingly utilized for diagnostic purposes in suspected Parkinsonian syndromes. We performed a cross-sectional study to investigate whether assessment of texture in DAT SPECT radiotracer uptake enables enhanced correlations with severity of motor and cognitive symptoms in Parkinson's disease (PD), with the long-term goal of enabling clinical utility of DAT SPECT imaging, beyond standard diagnostic tasks, to tracking of progression in PD. Quantitative analysis in routine DAT SPECT imaging, if performed at all, has been restricted to assessment of mean regional uptake...
2016: NeuroImage: Clinical
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