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https://www.readbyqxmd.com/read/29148542/prrt2-dependent-dyskinesia-cerebellar-paroxysmal-and-persistent
#1
Lieke Kros, Chris I De Zeeuw
In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia. PRRT2 turns out to downregulate the presynaptic SNARE complex in granule cell axons, which in turn controls the activity patterns of Purkinje cells, the sole output of the cerebellar cortex.
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29148391/outbreaks-of-neuroinvasive-astrovirus-associated-with-encephalomyelitis-weakness-and-paralysis-among-weaned-pigs-hungary
#2
Ákos Boros, Mihály Albert, Péter Pankovics, Hunor Bíró, Patricia A Pesavento, Tung Gia Phan, Eric Delwart, Gábor Reuter
A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29148209/telocytes-in-the-human-sinoatrial-node
#3
Lubov B Mitrofanova, Andrey N Gorshkov, Petr V Konovalov, Julia S Krylova
The sinoatrial node (SAN) is composed mostly of pacemaker, transitional and Purkinje-like cells. Pacemaker cells, especially in the centre of the SAN, are surrounded by dense fibrous tissue and do not have any contact with transitional cells. We hypothesize that the SAN contains telocytes that have contacts with pacemaker cells and contractile myocardium. Immunohistochemistry using antibodies against HCN4 and antibody combinations against CD34 and HCN4 was carried out on 12 specimens. Confocal laser scanning microscopy (CLSM) with two mixtures of primary antibodies, namely CD34/S100 and vimentin/S100, was performed in three cases...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29134361/sonic-hedgehog-agonist-protects-against-complex-neonatal-cerebellar-injury
#4
Vien Nguyen, Khalida Sabeur, Emin Maltepe, Kurosh Ameri, Omer Bayraktar, David H Rowitch
The cerebellum undergoes rapid growth during the third trimester and is vulnerable to injury and deficient growth in infants born prematurely. Factors associated with preterm cerebellar hypoplasia include chronic lung disease and postnatal glucocorticoid administration. We modeled chronic hypoxemia and glucocorticoid administration in neonatal mice to study whole cerebellar and cell type-specific effects of dual exposure. Chronic neonatal hypoxia resulted in permanent cerebellar hypoplasia. This was compounded by administration of prednisolone as shown by greater volume loss and Purkinje cell death...
November 13, 2017: Cerebellum
https://www.readbyqxmd.com/read/29134360/protein-kinase-c-in-the-cerebellum-its-significance-and-remaining-conundrums
#5
REVIEW
Hirokazu Hirai
Protein kinase C (PKC), a family of serine/threonine protein kinases, mediates a myriad of patho-physiological cellular events in various tissues. The originally discovered PKC (conventional) requires the binding of diacylglycerol and Ca(2+) for full activation. The conventional PKC consists of four isoforms, PKCα, PKCβI/βII, and PKCγ. PKCα and PKCβI/βII are expressed in the cells of various tissues including the brain, while PKCγ is present specifically in neurons of the brain and spinal cord. The cerebellum expresses the largest amount of PKC with all its four isoforms...
November 13, 2017: Cerebellum
https://www.readbyqxmd.com/read/29127138/%C3%AE-catenin-ctnnd2-missense-mutation-in-familial-cortical-myoclonic-tremor-and-epilepsy
#6
Anne-Fleur van Rootselaar, Alexander J Groffen, Boukje de Vries, Petra M C Callenbach, Gijs W E Santen, Stephany Koelewijn, Lisanne S Vijfhuizen, Arthur Buijink, Marina A J Tijssen, Arn M J M van den Maagdenberg
OBJECTIVE: To identify the causative gene in a large Dutch family with familial cortical myoclonic tremor and epilepsy (FCMTE). METHODS: We performed exome sequencing for 3 patients of our FCMTE family. Next, we performed knock-down (shRNA) and rescue experiments by overexpressing wild-type and mutant human δ-catenin (CTNND2) proteins in cortical mouse neurons and compared the results with morphologic abnormalities in the postmortem FCMTE brain. RESULTS: We identified a missense mutation, p...
November 10, 2017: Neurology
https://www.readbyqxmd.com/read/29116466/breast-cancer-related-paraneoplastic-neurologic-disease
#7
Brittany L Murphy, Nicholas L Zalewski, Amy C Degnim, Andrew McKeon, Eoin P Flanagan, Sean J Pittock, Elizabeth B Habermann
PURPOSE: Paraneoplastic neurologic disease (PND) is an aberrant immune-mediated response against the nervous system triggered by malignancy. Given the rarity, a paucity of data describing breast cancer-related PND (BC-PND) exists; we sought to further examine this specific patient population. METHODS: We retrospectively identified patients at our institution from 1997 to 2016 with BC-PND. Retrospective review with a descriptive analysis determined factors associated with PND and BC, which were compared to national breast cancer median of age (61 years) and average stage at diagnosis (60% local disease)...
November 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29115488/repeated-inhalation-of-sevoflurane-inhibits-the-information-transmission-of-purkinje-cells-and-delays-motor-development-via-the-gabaa-receptor-%C3%AE%C2%B5-subunit-in-neonatal-mice
#8
Hong Fang, Ze-Hua Wang, Ying-Jiang Bu, Zhi-Jun Yuan, Guo-Qiang Wang, Yan Guo, Xiao-Yun Cheng, Wen-Jie Qiu
General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ‑aminobutyric acidA receptor ε (GABAA‑R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29110208/expression-of-gas1-in-mouse-brain-release-and-role-in-neuronal-differentiation
#9
Elizabeth Bautista, Natanael Zarco, Nicolás Aguirre-Pineda, Manuel Lara-Lozano, Paula Vergara, Juan Antonio González-Barrios, Raúl Aguilar-Roblero, José Segovia
Growth arrest-specific 1 (Gas1) is a pleiotropic protein that induces apoptosis of tumor cells and has important roles during development. Recently, the presence of two forms of Gas1 was reported: one attached to the cell membrane by a GPI anchor; and a soluble extracellular form shed by cells. Previously, we showed that Gas1 is expressed in different areas of the adult mouse CNS. Here, we report the levels of Gas1 mRNA protein in different regions and analyzed its expressions in glutamatergic, GABAergic, and dopaminergic neurons...
November 6, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29106408/cell-type-specific-metabolic-labeling-of-nascent-proteomes-in-vivo
#10
Beatriz Alvarez-Castelao, Christoph T Schanzenbächer, Cyril Hanus, Caspar Glock, Susanne Tom Dieck, Aline R Dörrbaum, Ina Bartnik, Belquis Nassim-Assir, Elena Ciirdaeva, Anke Mueller, Daniela C Dieterich, David A Tirrell, Julian D Langer, Erin M Schuman
Although advances in protein labeling methods have made it possible to measure the proteome of mixed cell populations, it has not been possible to isolate cell-type-specific proteomes in vivo. This is because the existing methods for metabolic protein labeling in vivo access all cell types. We report the development of a transgenic mouse line where Cre-recombinase-induced expression of a mutant methionyl-tRNA synthetase (L274G) enables the cell-type-specific labeling of nascent proteins with a non-canonical amino-acid and click chemistry...
November 6, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29097665/rnf8-ubc13-ubiquitin-signaling-suppresses-synapse-formation-in-the-mammalian-brain
#11
Pamela Valnegri, Ju Huang, Tomoko Yamada, Yue Yang, Luis A Mejia, Ha Y Cho, Anna Oldenborg, Azad Bonni
Although ubiquitin ligases have been implicated in autism, their roles and mechanisms in brain development remain incompletely understood. Here, we report that in vivo knockdown or conditional knockout of the autism-linked ubiquitin ligase RNF8 or associated ubiquitin-conjugating enzyme UBC13 in rodent cerebellar granule neurons robustly increases the number of parallel fiber presynaptic boutons and functional parallel fiber/Purkinje cell synapses. In contrast to the role of nuclear RNF8 in proliferating cells, RNF8 operates in the cytoplasm in neurons to suppress synapse differentiation in vivo...
November 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/29079505/a-constitutively-active-ikk-complex-at-the-axon-initial-segment
#12
Hans-Georg König, Orla Watters, Sinéad Kinsella, Mohammed Ameen, Beau J Fenner, Jochen H M Prehn
BACKGROUND: Previous studies provided evidence for an accumulation of IκB-kinase (IKK) α/β at the axon initial segment (AIS), a neuronal compartment defined by ankyrin-G expression. Here we explored whether the presence of the IKK-complex at the AIS was associated with the activation of IKK signaling at this site. METHODS AND RESULTS: Proximity-ligation assays (PLAs) using pan-IKK α/β, phospho-IKK α/β -specific as well as ankyrin-G specific antibodies validated their binding to proximal epitopes in the AIS, while antibodies to other phosphorylated signaling proteins showed no preference for the AIS...
October 24, 2017: Brain Research
https://www.readbyqxmd.com/read/29079454/the-adenosine-a2a-receptor-agonist-t1-11-ameliorates-neurovisceral-symptoms-and-extends-the-lifespan-of-a-mouse-model-of-niemann-pick-type-c-disease
#13
Antonella Ferrante, Antonella Pezzola, Andrea Matteucci, Antonella Di Biase, Lucilla Attorri, Monica Armida, Alberto Martire, Yijuang Chern, Patrizia Popoli
Niemann-Pick C is a fatal neurovisceral disorder caused, in 95% of cases, by mutation of NPC1 gene. Therapeutic options are extremely limited and new "druggable" targets are highly warranted. We previously demonstrated that the stimulation of the adenosine A2A receptor (A2AR) normalized the pathological phenotype of cellular models of NPC1. Since the validation of A2ARs as a therapeutic target for NPC1 can be obtained only conducting studies in in vivo models of the disease, in the present paper, the effects of two agonists of A2ARs were evaluated in the mouse model Balb/c Npc1(nih), hereafter indicated as NPC1-/-...
October 25, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29078305/%C3%AE-iii-spectrin-spinocerebellar-ataxia-type-5-mutation-reveals-a-dominant-cytoskeletal-mechanism-that-underlies-dendritic-arborization
#14
Adam W Avery, David D Thomas, Thomas S Hays
A spinocerebellar ataxia type 5 (SCA5) L253P mutation in the actin-binding domain (ABD) of β-III-spectrin causes high-affinity actin binding and decreased thermal stability in vitro. Here we show in mammalian cells, at physiological temperature, that the mutant ABD retains high-affinity actin binding. Significantly, we provide evidence that the mutation alters the mobility and recruitment of β-III-spectrin in mammalian cells, pointing to a potential disease mechanism. To explore this mechanism, we developed a Drosophila SCA5 model in which an equivalent mutant Drosophila β-spectrin is expressed in neurons that extend complex dendritic arbors, such as Purkinje cells, targeted in SCA5 pathogenesis...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29072780/axonal-gabaa-receptors-depolarize-presynaptic-terminals-and-facilitate-transmitter-release-in-cerebellar-purkinje-cells
#15
Javier Zorrilla de San Martin, Federico F Trigo, Shin-Ya Kawaguchi
In neurons of the adult brain, somatodendritic GABAA Rs mediate fast synaptic inhibition and play a crucial role in synaptic integration. GABAA Rs are not only present in the somatodendritic compartment, but also in the axonal compartment where they modulate action potential (AP) propagation and transmitter release. Although presynaptic GABAA Rs have been reported in various brain regions, their mechanisms of action and physiological roles remain obscure, particularly at GABAergic boutons. Here, using a combination of direct whole-bouton or perforated patch-clamp recordings and local GABA photolysis in single axonal varicosities of cerebellar Purkinje cells, we investigate the subcellular localization and functional role of axonal GABAA Rs both in primary cultures and acute slices...
October 26, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29071065/logarithmic-distributions-prove-that-intrinsic-learning-is-hebbian
#16
Gabriele Scheler
In this paper, we document lognormal distributions for spike rates, synaptic weights and intrinsic excitability (gain) for neurons in various brain areas, such as auditory or visual cortex, hippocampus, cerebellum, striatum, midbrain nuclei. We find a remarkable consistency of heavy-tailed, specifically lognormal, distributions for rates, weights and gains in all brain areas. The difference between strongly recurrent and feed-forward connectivity (cortex vs. striatum and cerebellum), neurotransmitter (GABA (striatum) or glutamate (cortex)) or the level of activation (low in cortex, high in Purkinje cells and midbrain nuclei) turns out to be irrelevant for this feature...
2017: F1000Research
https://www.readbyqxmd.com/read/29070778/integrative-method-for-three-dimensional-imaging-of-the-entire-golgi-apparatus-by-combining-thiamine-pyrophosphatase-cytochemistry-and-array-tomography-using-backscattered-electron-mode-scanning-electron-microscopy
#17
Daisuke Koga, Satoshi Kusumi, Tatsuo Ushiki, Tsuyoshi Watanabe
Thiamine pyrophosphatase (TPPase) cytochemistry is an established method for specific labeling of the trans-Golgi cisterns in tissue sections. Herein, we combined this enzyme cytochemical method with array tomography using scanning electron microscopy (SEM), a new imaging technique based on collection of backscattered electron (BSE) images of consecutive resin-embedded sections on glass slides, to detect the entire three-dimensional (3D) organization of the Golgi apparatus with sufficient spatial resolution...
2017: Biomedical Research
https://www.readbyqxmd.com/read/29069799/functional-compatibility-between-purkinje-cell-axon-branches-and-their-target-neurons-in-the-cerebellum
#18
Zhilai Yang, Na Chen, Rongjing Ge, Hao Qian, Jin-Hui Wang
A neuron sprouts an axon, and its branches to innervate many target neurons that are divergent in their functions. In order to efficiently regulate the diversified cells, the axon branches should differentiate functionally to be compatible with their target neurons, i.e., a function compatibility between presynaptic and postsynaptic partners. We have examined this hypothesis by using electrophysiological method in the cerebellum, in which the main axon of Purkinje cell projected to deep nucleus cells and the recurrent axons innervated the adjacent Purkinje cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067089/is-biological-repair-of-heart-on-the-horizon
#19
REVIEW
H R Ahmad, Satwat Hashmi
The stem cells keep us young by endogenously repairing us upon need. They do so bysmartly one step forward towards differentiation while another step backward to nurturethe undifferentiated stem cells. They are building blocks for every organ witha differential rate of repair of worn out tissues. Since stem cells can be cultured with a normal karyo type, they could be the ideal source for heart repair after myocardial infarction. As opposed to lower vertebrates and neonatal mice, cardiac regeneration in adult mammalian heart seems to be difficult to assess with a solid evidence of cytokinesis...
July 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29066603/reminiscing-about-jan-evangelista-purkinje-a-pioneer-of-modern-experimental-physiology
#20
Icilio Cavero, Jean-Michel Guillon, Henry H Holzgrefe
This article reminisces about the life and key scientific achievements of Jan Evangelista Purkinje (1787-1869), a versatile 19th century Czech pioneer of modern experimental physiology. In 1804, after completing senior high school, Purkinje joined the Piarist monk order, but, after a 3-yr novitiate, he gave up the religious calling "to deal more freely with science." In 1818, he earned a Medical Doctor degree from Prague University by defending a dissertation on intraocular phenomena observed in oneself. In 1823, Purkinje became a Physiology and Pathology professor at the Prussian Medical University in Breslau, where he innovated the traditional teaching methods of physiology...
December 1, 2017: Advances in Physiology Education
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