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https://www.readbyqxmd.com/read/29330522/the-racgap-%C3%AE-chimaerin-is-essential-for-cerebellar-granule-cell-migration
#1
Jason A Estep, Wenny Wong, Yiu-Cheung E Wong, Brian M Loui, Martin M Riccomagno
During mammalian cerebellar development, postnatal granule cell progenitors proliferate in the outer part of the External Granule Layer (EGL). Postmitotic granule progenitors migrate tangentially in the inner EGL before switching to migrate radially inward, past the Purkinje cell layer, to achieve their final position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP β-chimaerin is expressed by a small population of late-born, premigratory granule cells. β-chimaerin deficiency causes a subset of granule cells to become arrested in the EGL, where they differentiate and form ectopic neuronal clusters...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#2
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29326173/transcriptional-regulator-zeb2-is-essential-for-bergmann-glia-development
#3
Li He, Kun Yu, Fanghui Lu, Jiajia Wang, Laiman N Wu, Chuntao Zhao, Qianmei Li, Xianyao Zhou, Hanmin Liu, Dezhi Mu, Mei Xin, Mengsheng Qiu, Q Richard Lu
Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson-syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical lamination dysgenesis and locomotion defects...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29326130/inward-rectifier-potassium-channels-kir2-x-and-caveolin-3-domain-specific-interaction-implications-for-purkinje-cell-dependent-ventricular-arrhythmias
#4
Ravi Vaidyanathan, Hanora Van Ert, Kazi T Haq, Stefano Morotti, Samuel Esch, Elise C McCune, Eleonora Grandi, Lee L Eckhardt
BACKGROUND: In human cardiac ventricle, IK1 is mainly comprised Kir2.1, but Kir2.2 and Kir2.3 heterotetramers occur and modulate IK1. Long-QT syndrome-9-associated CAV3 mutations cause decreased Kir2.1 current density, but Kir2.x heterotetramers have not been studied. Here, we determine the effect of long-QT syndrome-9-CAV3 mutation F97C on Kir2.x homo- and heterotetramers and model-associated arrhythmia mechanisms. METHODS AND RESULTS: Super-resolution microscopy, co-immunoprecipitation, cellular electrophysiology, on-cell Western blotting, and simulation of Purkinje and ventricular myocyte mathematical models were used...
January 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29323417/loss-of-ethanol-inhibition-of-nmdar-mediated-currents-and-plasticity-of-cerebellar-synapses-in-mice-expressing-the-glun1-f639a-subunit
#5
Paula A Zamudio-Bulcock, Gregg E Homanics, John J Woodward
BACKGROUND: Glutamatergic N-methyl-D-aspartate receptors (NMDARs) are well known for their sensitivity to ethanol inhibition. However, the specific manner in which ethanol inhibits channel activity and how such inhibition affects neurotransmission, and ultimately behavior, remain unclear. Replacement of phenylalanine 639 with alanine (F639A) in the GluN1 subunit reduces ethanol inhibition of recombinant NMDA receptors. Mice expressing this subunit show reduced ethanol-induced anxiolysis, blunted locomotor stimulation following low dose ethanol administration and faster recovery of motor function after moderate doses of ethanol suggesting that cerebellar dysfunction may contribute to some of these behaviors...
January 11, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29319237/regional-differences-in-purkinje-cell-morphology-in-the-cerebellar-vermis-of-male-mice
#6
Hermina Nedelescu, Mohamed Abdelhack, Arwel T Pritchard
Regional differences in dendritic architecture can influence connectivity and dendritic signal integration, with possible consequences for neuronal computation. In the cerebellum, analyses of Purkinje cells (PCs), which are functionally critical as they provide the sole output of the cerebellar cortex, have suggested that the cerebellar cortex is not uniform in structure as traditionally assumed. However, the limitations of traditional staining methods and microscopy capabilities have presented difficulties in investigating possible local variations in PC morphology...
January 10, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29307662/moringa-oleifera-phytochemicals-protect-the-brain-against-experimental-nicotine-induced-neurobehavioral-disturbances-and-cerebellar-degeneration
#7
Gabriel Olaiya Omotoso, Ismail Temitayo Gbadamosi, Olayemi Joseph Olajide, Shakirat Opeyemi Dada-Habeeb, Tolulope Timothy Arogundade, Emmanuel Olusola Yawson
Nicotine is a neuro-stimulant that has been implicated in the pathophysiology of many brain diseases. The need to prevent or alleviate the resulting dysfunction is therefore paramount, which has also given way to the use of medicinal plants in the management of brain conditions. This study was designed to determine the histomorphological and neurobehavioural changes in the cerebellum of Wistar rats following nicotine insult and how such injuries respond to Moringa intervention. Twenty-four adult male Wistar rats were divided into 4 groups...
January 4, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/29300895/multizonal-cerebellar-influence-over-sensorimotor-areas-of-the-rat-cerebral-cortex
#8
Sho Aoki, Patrice Coulon, Tom J H Ruigrok
The cerebral cortex requires cerebellar input for optimizing sensorimotor processing. However, how the sensorimotor cortex uses cerebellar information is far from understood. One critical and unanswered question is how cerebellar functional entities (zones or modules) are connected to distinct parts of the sensorimotor cortices. Here, we utilized retrograde transneuronal infection of rabies virus (RABV) to study the organization of connections from the cerebellar cortex to M1, M2, and S1 of the rat cerebral cortex...
December 29, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29297130/key-role-of-external-chloride-ions-in-regulation-of-fast-sodium-channels-in-rat-cerebellum-purkinje-neurons
#9
V L Zamoyski, V V Grigoriev
A decrease in the external chloride ion concentration to 4 mM caused a decrease in the fast sodium current to 85-100% in rat cerebellum Purkinje neurons in the whole-cell configuration using the patchclamp method. This effect did not depend on the main cation from the internal side of the cell membrane (120 mM of potassium or cesium) and also appeared when Cl- was substituted with sulfate (SO2-4) or phosphate (H2PO4-) anion outside of the cell. The effect was reversible after washing out the low chloride by the standard saline...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29285893/cerebellar-microglia-are-dynamically-unique-and-survey-purkinje-neurons-in-vivo
#10
Rianne D Stowell, Elissa L Wong, Hanna N Batchelor, Monique S Mendes, Cassandra E Lamantia, Brendan S Whitelaw, Ania K Majewska
Microglia are the innate immune cells of the central nervous system and are also important participants in normal development and synaptic plasticity. Here we demonstrate that the microglia of the mouse cerebellum represent a unique population compared to cortical microglia. Microglia are more sparsely distributed within the cerebellum and have a markedly less ramified morphology compared to their cortical counterparts. Using time-lapse in vivo imaging, we found that these differences in distribution and morphology ultimately lead to decreased parenchymal surveillance by cerebellar microglia...
December 29, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29282774/adult-moyamoya-disease-associated-with-abundant-phosphorylated-tau-accumulation-in-the-brainstem-report-of-a-case-with-autopsy-findings
#11
Koichi Okamoto, Isao Naito, Toshio Fukuda, Keiji Suzuki, Masamitsu Takatama
We report the case of a 72-year-old Japanese woman with moyamoya disease (MMD). She experienced her first intracerebral hemorrhage (ICH) at the age of 32 years, and had nine ICHs and/or intraventricular hemorrhages during the following 40 years. Cerebral angiograms and vascular pathologies at autopsy confirmed that the patient suffered from MMD. Macroscopically, there were brown-colored changes in the subarachnoid space, mainly at the base of the brain and around the cerebellar hemispheres. Microscopically, hemosiderin deposits were observed mainly in the old hemorrhagic lesions and on the surface of the brainstem and cerebellum...
December 27, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29282617/crus-i-in-the-rodent-cerebellum-its-homology-to-crus-i-and-ii-in-the-primate-cerebellum-and-its-anatomical-uniqueness-among-neighboring-lobules
#12
REVIEW
Izumi Sugihara
In the human cerebellum, the crus I and crus II lobules (or the ansiform lobule), which are implicated in cognitive and visuomotor functions, are significantly expanded compared to other anterior and posterior lobules, which are involved mainly in somatosensorimotor function. In applying rodent models, it is essential to identify the lobules that are homologous to human crus I and crus II. Observation of the lobular structure in human, macaque, marmoset, rat, and mouse has indicated that human crus I and II are homologous to crus I in rodents (referred to as "ansiform area, AA")...
December 27, 2017: Cerebellum
https://www.readbyqxmd.com/read/29282276/the-neuron-specific-formin-delphilin-nucleates-non-muscle-actin-but-does-not-enhance-elongation
#13
William T Silkworth, Kristina L Kunes, Grace C Nickel, Martin L Phillips, Margot E Quinlan, Christina L Vizcarra
The formin Delphilin binds the glutamate receptor, GluRδ2, in dendritic spines of Purkinje cells. Both proteins play a role in learning. To understand how Delphilin functions in neurons, we studied the actin assembly properties of this formin. Formins have a conserved formin homology 2 domain, which nucleates and associates with the fast growing end of actin filaments, influencing filament growth together with the formin homology 1 (FH1) domain. The strength of nucleation and elongation varies widely across formins...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29251109/human-olfactory-ensheathing-cell-transplantation-improves-motor-function-in-a-mouse-model-of-type-3-spinocerebellar-ataxia
#14
Jeanne Hsieh, Jen-Wei Liu, Horng-Jyh Harn, Kuo-Wei Hsueh, Karthyayani Rajamani, Yu-Chen Deng, Chih-Min Chia, Woei-Cheang Shyu, Shinn-Zong Lin, Tzyy-Wen Chiou
Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease that affects the cerebellum and spinal cord. Among the 40 types of SCA, SCA type 3 (SCA3), also referred to as Machado-Joseph disease, is the most common. In the present study, we investigated the therapeutic effects of intracranial transplantation of human olfactory ensheathing cells (hOECs) in the ATXN3-84Q mouse model of SCA3. Motor function begins to decline in ATXN3-84Q transgenic mice at approximately 13 weeks of age. ATXN3-84Q mice that received intracranial hOEC transplantation into the dorsal raphe nucleus of the brain exhibited significant improvements in motor function, as measured by the rotarod performance test and footprint pattern analysis...
October 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29249942/secretin-modulates-the-postnatal-development-of-mouse-cerebellar-cortex-via-pka-and-erk-dependent-pathways
#15
Lei Wang, Li Zhang, Billy K C Chow
Postnatal development of the cerebellum is critical for its intact function such as motor coordination and has been implicated in the pathogenesis of psychiatric disorders. We previously reported that deprivation of secretin (SCT) from cerebellar Purkinje neurons impaired motor coordination and motor learning function, while leaving the potential role of SCT in cerebellar development to be determined. SCT and its receptor (SCTR) were constitutively expressed in the postnatal cerebellum in a temporal and cell-specific manner...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29249940/propofol-exposure-in-early-life-induced-developmental-impairments-in-the-mouse-cerebellum
#16
Rui Xiao, Dan Yu, Xin Li, Jing Huang, Sheng Jing, Xiaohang Bao, Tiande Yang, Xiaotang Fan
Propofol is a widely used anesthetic in the clinic while several studies have demonstrated that propofol exposure may cause neurotoxicity in the developing brain. However, the effects of early propofol exposure on cerebellar development are not well understood. Propofol (30 or 60 mg/kg) was administered to mice on postnatal day (P)7; Purkinje cell dendritogenesis and Bergmann glial cell development were evaluated on P8, and granule neuron migration was analyzed on P10. The results indicated that exposure to propofol on P7 resulted in a significant reduction in calbindin-labeled Purkinje cells and their dendrite length...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29249302/motor-learning-induces-plastic-changes-in-purkinje-cell-dendritic-spines-in-the-rat-cerebellum
#17
D González-Tapia, M M González-Ramírez, N Vázquez-Hernández, I González-Burgos
INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method...
December 14, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29243588/dynamic-modulation-of-activity-in-cerebellar-nuclei-neurons-during-pavlovian-eyeblink-conditioning-in-mice
#18
Michiel Manuel Ten Brinke, Shane Heiney, Xiaolu Wang, Martina Proietti-Onori, Henk-Jan Boele, Jacob Bakermans, Javier F Medina, Zhenyu Gao, Chris I De Zeeuw
While research on the cerebellar cortex is crystallizing our understanding of its function in learning behavior, many questions surrounding its downstream targets remain. Here, we evaluate the dynamics of cerebellar interpositus nucleus (IpN) neurons over the course of Pavlovian eyeblink conditioning. A diverse range of learning-induced neuronal responses was observed, including increases and decreases in activity during the generation of conditioned blinks. Trial-by-trial correlational analysis and optogenetic manipulation demonstrate that facilitation in the IpN drives the eyelid movements...
December 15, 2017: ELife
https://www.readbyqxmd.com/read/29221819/cerebellar-alterations-in-a-model-of-down-syndrome-the-role-of-the-dyrk1a-gene
#19
Susana García-Cerro, Verónica Vidal, Sara Lantigua, Maria Teresa Berciano, Miguel Lafarga, Pedro Ramos-Cabrer, Daniel Padro, Noemí Rueda, Carmen Martínez-Cué
Down syndrome (DS) is characterized by a marked reduction in the size of the brain and cerebellum. These changes play an important role in the motor alterations and cognitive disabilities observed in this condition. The Ts65Dn (TS) mouse, the most commonly used model of DS, reflects many DS phenotypes, including alterations in cerebellar morphology. One of the genes that is overexpressed in both individuals with DS and TS mice is DYRK1A/Dyrk1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which has been implicated in the altered cerebellar structural and functional phenotypes observed in both populations...
December 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29213114/the-swi-snf-subunit-bcl7a-contributes-to-motor-coordination-and-purkinje-cell-function
#20
Lena Wischhof, Simona Maida, Antonia Piazzesi, Anna Gioran, Kristina Barragan Sanz, Stephan Irsen, Marc Beyer, Joachim L Schultze, Martin J Dyer, Paolo Salomoni, Dan Ehninger, Pierluigi Nicotera, Daniele Bano
Chromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain. We generated ubiquitous and neuron-specific Bcl7a and Bcl7b single and double knockout mice...
December 6, 2017: Scientific Reports
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