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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
#1
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/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#2
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28219193/-analysis-of-ct-perfusion-imaging-in-chronic-cerebral-circulatory-insufficiency-and-its-relationship-with-crossed-cerebellar-diaschisis
#3
S L Liu, Y Wang, Y Zhang, H L Xu, J C Wang, W W He, X T Qin, G Q Cao, Y J Yang, Q C Zhuge, W J Chen
Objective: To investigate the change of cerebral microcirculation of chronic cerebral circulation insufficiency(CCCI) patients and the relationship between CCCI and crossed cerebellar diaschisis(CCD)by using 320-detector row of low-dose volume CT perfusion imaging. Methods: A total of 158 patients (103 males, 55 females, from 45 to 82 years old, the mean age was 62.9) with symptoms of CCCI were admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2013 to January 2016. Low-dose CTP imaging of whole brain was performed to them using 320-detector row volume CT scanner...
February 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28198698/a-role-for-cerebellum-in-the-hereditary-dystonia-dyt1
#4
Rachel Fremont, Ambika Tewari, Chantal Angueyra, Kamran Khodakhah
DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential development compensation between rodents and humans. To address this issue, torsinA was acutely knocked down in select brain regions of adult mice using shRNAs. TorsinA knockdown in the cerebellum, but not in the basal ganglia, was sufficient to induce dystonia...
February 15, 2017: ELife
https://www.readbyqxmd.com/read/28193688/compulsive-social-behavior-emerges-after-selective-ablation-of-striatal-cholinergic-interneurons
#5
Yanina V Martos, Barbara Y Braz, Juan P Beccaria, M Gustavo Murer, Juan E Belforte
The mechanisms underlying social dysfunction in neuropsychiatric conditions like obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions in basal ganglia, including reduced number of striatal cholinergic interneurons (SCIN), have been involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type and region specific manner...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28192762/neural-mass-models-describing-possible-origin-of-the-excessive-beta-oscillations-correlated-with-parkinsonian-state
#6
Chen Liu, Yulin Zhu, Fei Liu, Jiang Wang, Huiyan Li, Bin Deng, Chris Fietkiewicz, Kenneth A Loparo
In Parkinson's disease, the enhanced beta rhythm is closely associated with akinesia/bradykinesia and rigidity. An increase in beta oscillations (12-35 Hz) within the basal ganglia (BG) nuclei does not proliferate throughout the cortico-basal ganglia loop in uniform fashion; rather it can be subdivided into two distinct frequency bands, i.e. the lower beta (12-20 Hz) and upper beta (21-35 Hz). A computational model of the excitatory and inhibitory neural network that focuses on the population properties is proposed to explore the mechanism underlying the pathological beta oscillations...
January 30, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28190394/neuroprotective-effect-of-atremorine-in-an-experimental-model-of-parkinson%C3%A2-s-disease
#7
Ivan Carrera, Lucia Fernandez-Novoa, Carolina Sampedro, Ramon Cacabelos
Parkinsonian-like state was generated in mice by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to study the effects of Atremorine in Parkinson's disease (PD) related neuropathology and behavior deficits. This devastating disease is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra. Numerous therapeutic strategies have been developed to protect neuronal damage, although no effective treatment for PD has been validated yet. This study tested the preventive and therapeutic neuroprotective effect of Atremorine on MPTP parkinsonian mouse model...
February 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28182673/the-expanded-cag-repeat-in-the-huntingtin-gene-as-target-for-therapeutic-rna-modulation-throughout-the-hd-mouse-brain
#8
Nicole A Datson, Anchel González-Barriga, Eleni Kourkouta, Rudie Weij, Jeroen van de Giessen, Susan Mulders, Outi Kontkanen, Taneli Heikkinen, Kimmo Lehtimäki, Judith C T van Deutekom
The aim of these studies was to demonstrate the therapeutic capacity of an antisense oligonucleotide with the sequence (CUG)7 targeting the expanded CAG repeat in huntingtin (HTT) mRNA in vivo in the R6/2 N-terminal fragment and Q175 knock-in Huntington's disease (HD) mouse models. In a first study, R6/2 mice received six weekly intracerebroventricular infusions with a low and high dose of (CUG)7 and were sacrificed 2 weeks later. A 15-60% reduction of both soluble and aggregated mutant HTT protein was observed in striatum, hippocampus and cortex of (CUG)7-treated mice...
2017: PloS One
https://www.readbyqxmd.com/read/28154122/measurement-of-lactate-content-and-amide-proton-transfer-values-in-the-basal-ganglia-of-a-neonatal-piglet-hypoxic-ischemic-brain-injury-model-using-mri
#9
Y Zheng, X-M Wang
BACKGROUND AND PURPOSE: As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. MATERIALS AND METHODS: From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1...
February 2, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28137879/differentiation-of-human-telencephalic-progenitor-cells-into-msns-by-inducible-expression-of-gsx2-and-ebf1
#10
Andrea Faedo, Angela Laporta, Alice Segnali, Maura Galimberti, Dario Besusso, Elisabetta Cesana, Sara Belloli, Rosa Maria Moresco, Marta Tropiano, Elisa Fucà, Stefan Wild, Andreas Bosio, Alessandro E Vercelli, Gerardo Biella, Elena Cattaneo
Medium spiny neurons (MSNs) are a key population in the basal ganglia network, and their degeneration causes a severe neurodegenerative disorder, Huntington's disease. Understanding how ventral neuroepithelial progenitors differentiate into MSNs is critical for regenerative medicine to develop specific differentiation protocols using human pluripotent stem cells. Studies performed in murine models have identified some transcriptional determinants, including GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1)...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28132829/studying-brain-circuit-function-with-dynamic-causal-modeling-for-optogenetic-fmri
#11
David Bernal-Casas, Hyun Joo Lee, Andrew J Weitz, Jin Hyung Lee
Defining the large-scale behavior of brain circuits with cell type specificity is a major goal of neuroscience. However, neuronal circuit diagrams typically draw upon anatomical and electrophysiological measurements acquired in isolation. Consequently, a dynamic and cell-type-specific connectivity map has never been constructed from simultaneous measurements across the brain. Here, we introduce dynamic causal modeling (DCM) for optogenetic fMRI experiments-which uniquely allow cell-type-specific, brain-wide functional measurements-to parameterize the causal relationships among regions of a distributed brain network with cell type specificity...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28130586/gene-therapy-approaches-in-the-non-human-primate-model-of-parkinson-s-disease
#12
REVIEW
D Pignataro, D Sucunza, A J Rico, I G Dopeso-Reyes, E Roda, A I Rodríguez-Perez, J L Labandeira-Garcia, V Broccoli, S Kato, K Kobayashi, José L Lanciego
The field of gene therapy has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify basal ganglia circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by gene-induced changes in brain circuits. Among others, at present, it is technically feasible to use viral vectors to (1) achieve a controlled release of neurotrophic factors, (2) conduct either a transient or permanent silencing of any given basal ganglia circuit of interest, (3) perform an in vivo cellular reprogramming by promoting the conversion of resident cells into dopaminergic-like neurons, and (4) improving levodopa efficacy over time by targeting aromatic L-amino acid decarboxylase...
January 27, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28124435/current-applications-and-limitations-of-surgical-treatments-for-movement-disorders
#13
REVIEW
Paul Krack, Raul Martinez-Fernandez, Marta Del Alamo, Jose A Obeso
Functional neurosurgery for the treatment of both psychiatric and neurological disorders has been performed regularly since the 1940s. However, misuse in the early days and the appearance of effective medical treatments, such as levodopa and neuroleptic drugs, greatly reduced surgical approaches over several decades. The development of a comprehensive model of basal ganglia pathophysiology in the 1990s facilitated the resurgence of functional neurosurgery, mainly for the treatment of levodopa-related motor complications in Parkinson's disease...
January 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28122201/in%C3%A2-vivo-measurement-of-pde10a-enzyme-occupancy-by-positron-emission-tomography-pet-following-single-oral-dose-administration-of-pf-02545920-in-healthy-male-subjects
#14
Marielle Delnomdedieu, Anton Forsberg, Adam Ogden, Patrik Fazio, Ching-Ray Yu, Per Stenkrona, Sridhar Duvvuri, William David, Nabil Al-Tawil, Ottavio V Vitolo, Nahid Amini, Sangram Nag, Christer Halldin, Andrea Varrone
Phosphodiesterase 10A (PDE10A) is an enzyme highly enriched in the striatal medium spiny neurons. It is involved in the regulation of cytoplasmic levels of cAMP and cGMP and signaling within the basal ganglia. This study with PDE10A radioligand [(18)F]MNI-659 was designed to measure the enzyme occupancy of PF-02545920 in 8 healthy male volunteers (48 ± 4 years) after a single oral dose (10 mg or 20 mg) and to evaluate safety and tolerability. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function for the quantification of [(18)F]MNI-659 binding to PDE10A...
January 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28118848/the-association-of-findings-on-brain-computed-tomography-with-neurologic-outcomes-following-extracorporeal-cardiopulmonary-resuscitation
#15
Jeong-Am Ryu, Chi Ryang Chung, Yang Hyun Cho, Kiick Sung, Gee Young Suh, Taek Kyu Park, Young Bin Song, Joo-Yong Hahn, Jin-Ho Choi, Hyeon-Cheol Gwon, Seung-Hyuk Choi, Jeong Hoon Yang
BACKGROUND: Limited data are available on imaging predictors of neurological outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). We investigated the association of initial brain computed tomography (CT) findings with neurological outcomes following ECPR. METHODS: Between February 2005 and December 2015, a total of 42 patients who underwent brain CT scans within 48 h after ECPR were analyzed. Loss of the boundary between gray matter and white matter (LOB) or cortical sulcal effacement (SE), gray-to-white matter ratio (GWR), and optic nerve sheath diameter (ONSD) were measured on initial brain CT...
January 25, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28115486/phosphodiesterase-10a-opposite-changes-in-striato-pallidal-and-striato-entopeduncular-pathways-of-a-transgenic-mouse-model-of-dyt1-dystonia
#16
V D'Angelo, V Castelli, M Giorgi, S Cardarelli, I Saverioni, F Palumbo, P Bonsi, A Pisani, C Giampà, R Sorge, S Biagioni, F R Fusco, G Sancesario
: We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 and inhibited by D2 receptors, expressed in striato-entopeducuncular/substantia nigra or striato-pallidal pathways, respectively.PDE10A was studied in control mice (NT), and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT)...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28113673/uncertainty-quantification-of-oscillation-suppression-during-dbs-in-a-coupled-finite-element-and-network-model
#17
Christian Schmidt, Eleanor Dunn, Madeleine Lowery, Ursula van Rienen
Models of the cortico-basal ganglia network and volume conductor models of the brain can provide insight into the mechanisms of action of deep brain stimulation (DBS). In this study, the coupling of a network model, under parkinsonian conditions, to the extracellular field distribution obtained from a three dimensional finite element model of a rodent's brain during DBS is presented. This coupled model is used to investigate the influence of uncertainty in the electrical properties of brain tissue and encapsulation tissue, formed around the electrode after implantation, on the suppression of oscillatory neural activity during DBS...
September 13, 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#18
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28098719/regional-gray-matter-volumes-as-related-to-psychomotor-slowing-in-adults-with-type-1-diabetes
#19
Karen A Nunley, Christopher M Ryan, Howard J Aizenstein, Rebecca L MacCloud, Trevor J Orchard, Caterina Rosano
OBJECTIVE: Psychomotor slowing is a common cognitive complication in type 1 diabetes (T1D), but its neuroanatomical correlates and risk factors are unclear. In non-diabetic adults, smaller gray matter volume (GMV) and presence of white matter hyperintensities (WMH) are associated with psychomotor slowing. We hypothesize that smaller GMV in prefronto-parietal regions explains T1D-related psychomotor slowing. We also inspect the contribution of microvascular disease and hyperglycemia. METHODS: GMV, WMH, and glucose levels were measured concurrently with a test of psychomotor speed (Digit Symbol Substitution Test, DSST) in 95 adults with childhood-onset T1D (mean age/duration=49/41 years) and 135 similarly-aged non-T1D adults...
January 17, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28073788/dopamine-controls-parkinson-s-tremor-by-inhibiting-the-cerebellar-thalamus
#20
Michiel F Dirkx, Hanneke E M den Ouden, Esther Aarts, Monique H M Timmer, Bastiaan R Bloem, Ivan Toni, Rick C Helmich
Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor...
January 9, 2017: Brain: a Journal of Neurology
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