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https://www.readbyqxmd.com/read/29785638/intermittent-convection-enhanced-delivery-of-gdnf-into-rhesus-monkey-putamen-absence-of-local-or-cerebellar-toxicity
#1
Matthias Luz, Philip C Allen, John Bringas, Chris Boiko, Diane E Stockinger, Kristen J Nikula, Owen Lewis, Max Woolley, H Christian Fibiger, Krystof Bankiewicz, Erich Mohr
Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions...
May 22, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29784481/intraventricular-delay-and-blocks
#2
REVIEW
Fabio M Leonelli, Giuseppe Bagliani, Roberto De Ponti, Luigi Padeletti
From the atrioventricular node, electrical activation is propagated to both ventricles by a system of specialized conducting fibers, His Purkinje System (HPS), guaranteeing a fast, synchronous depolarization of both ventricles. From the predivisional common stem, a right and left branch separate, subdividing further in a fairly predictable fashion. Synchronous ventricular activation results in a QRS with specific characteristics and duration of less than 110 milliseconds. Block or delay in any part of the HPS changes the electrocardiographic (ECG) morphology...
June 2018: Cardiac Electrophysiology Clinics
https://www.readbyqxmd.com/read/29779650/streamlined-method-for-anchoring-cataract-surgery-and-intraocular-lens-centration-on-the-patient-s-visual-axis
#3
Vance Thompson
I describe an intraoperative method for the consistent anchoring of the intraocular lens (IOL) and cataract surgery and on the patient's visual axis using coaxial microscope optics, surgeon-guided patient fixation, the precision pulse capsulotomy (PPC) device (Zepto) and utilizing the first (and fourth) Purkinje images. During surgery using a microscope with coaxial lights and optics, the patient is instructed to fixate on a given microscope light while the surgeon looks through the corresponding coaxial eyepiece...
May 17, 2018: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/29777722/ca-2-signaling-and-spinocerebellar-ataxia
#4
REVIEW
Chihiro Hisatsune, Kozo Hamada, Katsuhiko Mikoshiba
Spinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with >35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating evidence supports the occurrence of a common pathophysiological event among several hereditary SCAs...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774619/different-types-of-multiple-synapse-boutons-in-the-cerebellar-cortex-between-physically-enriched-and-ataxic-mutant-mice
#5
Hyun-Wook Kim, Seunghak Oh, Seung Hwan Lee, Sanghoon Lee, Ji-Eun Na, Kea Joo Lee, Im Joo Rhyu
Experience-dependent synapse remodeling is associated with information storage in the nervous system. Neuronal synapses show alteration in various neurological and cognitive disorders in their structure and function. At the ultrastructural level, parallel fiber boutons contacting multiple spines of Purkinje cells in the cerebellar cortex are commonly observed in physiologically enriched animals as well as pathological ataxic mutants. However, the dendritic origin of those spines on parallel fiber multiple-synapse boutons (MSBs) has been poorly understood...
May 18, 2018: Microscopy Research and Technique
https://www.readbyqxmd.com/read/29772246/preterm-birth-disrupts-cerebellar-development-by-affecting-granule-cell-proliferation-program-and-bergmann-glia
#6
Igor Y Iskusnykh, Randal K Buddington, Victor V Chizhikov
Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants...
May 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29769718/ankrd16-prevents-neuron-loss-caused-by-an-editing-defective-trna-synthetase
#7
My-Nuong Vo, Markus Terrey, Jeong Woong Lee, Bappaditya Roy, James J Moresco, Litao Sun, Hongjun Fu, Qi Liu, Thomas G Weber, John R Yates, Kurt Fredrick, Paul Schimmel, Susan L Ackerman
Editing domains of aminoacyl tRNA synthetases correct tRNA charging errors to maintain translational fidelity. A mutation in the editing domain of alanyl tRNA synthetase (AlaRS) in Aars sti mutant mice results in an increase in the production of serine-mischarged tRNAAla and the degeneration of cerebellar Purkinje cells. Here, using positional cloning, we identified Ankrd16, a gene that acts epistatically with the Aars sti mutation to attenuate neurodegeneration. ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29765353/fentanyl-induces-cerebellar-internal-granular-cell-layer-apoptosis-in-healthy-newborn-pigs
#8
Hemmen Sabir, John Dingley, Emma Scull-Brown, Ela Chakkarapani, Marianne Thoresen
Background: Opioids like fentanyl are regularly used in neonates for analgesia and sedation. So far, they have been reported to be safe and eligible to use. The cerebellum has become a focus of neurodevelopmental research within the last years, as it is known to play an important role in long-lasting motor, cognitive, and other behavioral changes. The cerebellar cortex is of major importance in the coordinative role of the cerebellum and highly vulnerable to injury and impaired growth...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29763885/intrauterine-growth-restriction-affects-cerebellar-granule-cells-in-the-developing-guinea-pig-brain
#9
Mary Tolcos, Annie McDougall, Amy Shields, Yoonyoung Chung, Rachael O'Dowd, Ann Turnley, Megan Wallace, Sandra Rees
Intrauterine growth restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. However, the effects of IUGR on the cerebellum are still to be fully elucidated. A major determinant of growth and development of the cerebellum is proliferation and subsequent migration of cerebellar granule cells. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in guinea pigs, results in abnormal cerebellar development due to deficits suggestive of impaired granule cell proliferation and/or migration...
May 15, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29762671/motor-impairments-correlate-with-social-deficits-and-restricted-neuronal-loss-in-an-environmental-model-of-autism
#10
Tareq Al Sagheer, Obelia Haida, Anais Balbous, Maureen Francheteau, Emmanuel Matas, Pierre-Olivier Fernagut, Mohamed Jaber
Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders (ASD) but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods: Here, we aimed at determining whether a well-acknowledged animal model of ASD, the valproic acid (VPA) model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas...
May 12, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29760657/purkinje-cell-signaling-deficits-in-animal-models-of-ataxia
#11
REVIEW
Eriola Hoxha, Ilaria Balbo, Maria Concetta Miniaci, Filippo Tempia
Purkinje cell (PC) dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction...
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29759663/cellular-physiology-and-clinical-manifestations-of-fascicular-arrhythmias-in-normal-hearts
#12
REVIEW
Raphael K Sung, Penelope A Boyden, Melvin Scheinman
Fascicular ventricular arrhythmias represent a spectrum of ventricular tachycardias dependent on the specialized conduction system. Although they are more common in structurally abnormal hearts, there is an increasing body of literature describing their role in normal hearts. In this review, the authors present data from both basic and clinical research that explore the current understanding of idiopathic fascicular ventricular arrhythmias. Evaluation of the cellular electrophysiology of the Purkinje cells shows clear evidence of enhanced automaticity and triggered activity as potential mechanisms of arrhythmias...
December 11, 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/29759535/utility-of-conventional-electrocardiographic-criteria-in-patients-with-idiopathic-ventricular-tachycardia
#13
Anil V Yadav, Babak Nazer, Barbara J Drew, John M Miller, Hicham El Masry, William J Groh, Andrea Natale, Nassir Marrouche, Nitish Badhwar, Yanfei Yang, Melvin M Scheinman
OBJECTIVES: This study sought to determine the ability of conventional electrocardiographic (ECG) criteria to correctly differentiate idiopathic ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrancy. BACKGROUND: Previously reported VT ECG criteria were developed from cohorts of patients with structural heart disease and have not been applied to patients with idiopathic VT. METHODS: ECGs of 115 idiopathic VTs, 101 post-myocardial infarction (MI) VTs, and 111 wide QRS SVTs were analyzed using standard criteria...
July 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/29758256/reduction-of-protein-kinase-a-mediated-phosphorylation-of-atxn1-s776-in-purkinje-cells-delays-onset-of-ataxia-in-a-sca1-mouse-model
#14
Judit M Pérez Ortiz, Nissa Mollema, Nicholas Toker, Carolyn J Adamski, Brennon O'Callaghan, Lisa Duvick, Jillian Friedrich, Michael A Walters, Jessica Strasser, Jon E Hawkinson, Huda Y Zoghbi, Christine Henzler, Harry T Orr, Sarita Lagalwar
Spinocerebellar ataxia type 1 (SCA1) is a polyglutamine (polyQ) repeat neurodegenerative disease in which a primary site of pathogenesis are cerebellar Purkinje cells. In addition to polyQ expansion of ataxin-1 protein (ATXN1), phosphorylation of ATXN1 at the serine 776 residue (ATXN1-pS776) plays a significant role in protein toxicity. Utilizing a biochemical approach, pharmacological agents and cell-based assays, including SCA1 patient iPSC-derived neurons, we examine the role of Protein Kinase A (PKA) as an effector of ATXN1-S776 phosphorylation...
May 11, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29753755/polarization-sensitive-optical-coherence-tomography-reveals-gray-matter-and-white-matter-atrophy-in-sca1-mouse-models
#15
Chao J Liu, Orion Rainwater, H Brent Clark, Harry T Orr, Taner Akkin
Spinocerebellar ataxia type 1 (SCA1) is a fatal inherited neurodegenerative disease. In this study, we demonstrate the label-free optical imaging methodology that can detect, with a high degree of sensitivity, discrete areas of degeneration in the cerebellum of the SCA1 mouse models. We used ATXN1[82Q] and ATXN1[30Q]-D776 mice in which the transgene is directed only to Purkinje cells. Molecular layer, granular layer, and white matter regions are analyzed using the intrinsic contrasts provided by polarization-sensitive optical coherence tomography...
May 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29746896/insights-into-cerebellar-development-and-connectivity
#16
REVIEW
Jaclyn Beckinghausen, Roy V Sillitoe
The cerebellum has a well-established role in controlling motor functions such coordination, balance, posture, and skilled learning. There is mounting evidence that it might also play a critical role in non-motor functions such as cognition and emotion. It is therefore not surprising that cerebellar deficits are associated with a wide array of diseases including ataxia, dystonia tremor, schizophrenia, dyslexia, and autism spectrum disorder. What is intriguing is that a seemingly uniform circuit that is often described as being "simple" should carry out all of these behaviors...
May 7, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29744592/biology-and-pathology-of-perineuronal-satellite-cells-in-sensory-ganglia
#17
Ennio Pannese
A cell sheath enveloping the body of the neurons in sensory ganglia was mentioned for the first time in 1836 by Valentin, a pupil of Purkinje. In some illustrations of his paper, the nuclei of cells adjacent to the surface of the nerve cell body, both in the trigeminal ganglion and in the ganglia of the autonomic nervous system, were clearly shown (Fig. 1.1a) even though they were misinterpreted as pigment granules. Since Remak (1838) denied the existence of this perineuronal sheath, Valentin (1839) provided a more detailed description of it, illustrated with new drawings (Fig...
2018: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/29741614/loss-of-cerebellar-glutamate-transporters-eaat4-and-glast-differentially-affects-the-spontaneous-firing-pattern-and-survival-of-purkinje-cells
#18
Emma M Perkins, Yvonne L Clarkson, Daumante Suminaite, Alastair R Lyndon, Kohichi Tanaka, Jeffrey D Rothstein, Paul Skehel, David J A Wyllie, Mandy Jackson
Loss of excitatory amino acid transporters (EAATs) has been implicated in a number of human diseases including spinocerebellar ataxias, Alzhiemer's disease and motor neuron disease. EAAT4 and GLAST/EAAT1 are the two predominant EAATs responsible for maintaining low extracellular glutamate levels and preventing neurotoxicity in the cerebellum, the brain region essential for motor control. Here using genetically modified mice we identify new critical roles for EAAT4 and GLAST/EAAT1 as modulators of Purkinje cell (PC) spontaneous firing patterns...
May 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29739992/conduction-in-the-heart-wall-helicoidal-fibers-minimize-diffusion-bias
#19
Tristan Aumentado-Armstrong, Amir Kadivar, Peter Savadjiev, Steven W Zucker, Kaleem Siddiqi
The mammalian heart must function as an efficient pump while simultaneously conducting electrical signals to drive the contraction process. In the ventricles, electrical activation begins at the insertion points of the Purkinje network in the endocardium. How does the diffusion component of the subsequent excitation wave propagate from the endocardium in a healthy heart wall without creating directional biases? We show that this is a consequence of the particular geometric organization of myocytes in the heart wall...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739131/intravenous-anesthetic-propofol-affects-synaptic-responses-in-cerebellar-purkinje-cells
#20
Kwan Young Lee, Yujin Jang, Min Hee Lee, Young Im Kim, Sung-Cherl Jung, Seung-Yun Han, Se Hoon Kim, Hyung Seo Park, Dong Kwan Kim
Objective: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. Methods: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques...
May 31, 2018: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
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