keyword
MENU ▼
Read by QxMD icon Read
search

Q175

keyword
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
#1
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/28031289/attenuated-pupillary-light-responses-and-downregulation-of-opsin-expression-parallel-decline-in-circadian-disruption-in-two-different-mouse-models-of-huntington-s-disease
#2
Koliane Ouk, Steven Hughes, Carina A Pothecary, Stuart N Peirson, A Jennifer Morton
Circadian deficits in Huntington's disease (HD) are recapitulated in both fragment (R6/2) and full-length (Q175) mouse models of HD. Circadian rhythms are regulated by the suprachiasmatic nuclei (SCN) in the hypothalamus, which are primarily entrained by light detected by the retina. The SCN receives input from intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin, but also receive input from rods and cones. In turn, ipRGCs mediate a range of non-image forming responses to light including circadian entrainment and the pupillary light response (PLR)...
December 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28018188/cholinergic-interneurons-amplify-corticostriatal-synaptic-responses-in-the-q175-model-of-huntington-s-disease
#3
Asami Tanimura, Sean Austin O Lim, Jose de Jesus Aceves Buendia, Joshua A Goldberg, D James Surmeier
Huntington's disease (HD) is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs) are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice...
2016: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/27995895/early-dysfunction-and-progressive-degeneration-of-the-subthalamic-nucleus-in-mouse-models-of-huntington-s-disease
#4
Jeremy F Atherton, Eileen L McIver, Matthew Rm Mullen, David L Wokosin, D James Surmeier, Mark D Bevan
The subthalamic nucleus (STN) is an element of cortico-basal ganglia-thalamo-cortical circuitry critical for action suppression. In Huntington's disease (HD) action suppression is impaired, resembling the effects of STN lesioning or inactivation. To explore this potential linkage, the STN was studied in BAC transgenic and Q175 knock-in mouse models of HD. At <2 and 6 months of age autonomous STN activity was impaired due to activation of KATP channels. STN neurons exhibited prolonged NMDA receptor-mediated synaptic currents, caused by a deficit in glutamate uptake, and elevated mitochondrial oxidant stress, which was ameliorated by NMDA receptor antagonism...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27989734/systemic-application-of-aav-vectors-targeting-gfap-expressing-astrocytes-in-z-q175-ki-huntington-s-disease-mice
#5
Tatyana Vagner, Anton Dvorzhak, Anna Maria Wójtowicz, Christoph Harms, Rosemarie Grantyn
Huntington's disease (HD) affects both neurons and astrocytes. To target the latter and to ensure brain-wide transgene expression, adeno-associated viral (AAV) vectors can be administered intravenously, as AAV vectors cross the blood-brain barrier (BBB) and enable preferential transduction of astrocytes due to their close association with blood vessels. However, there is a possibility that the subclass of GFAP-expressing astrocytes performs a distinct role in HD and reacts differently to therapeutic measures than the rest of the astrocytes...
October 27, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27938392/ulk1-mediated-phosphorylation-of-atg14-promotes-autophagy-and-is-impaired-in-huntington-s-disease-models
#6
Mitchell S Wold, Junghyun Lim, Véronik Lachance, Zhiqiang Deng, Zhenyu Yue
BACKGROUND: Autophagy is a bulk degradation pathway for long-lived proteins, protein aggregates, and damaged organelles. ULK1 protein kinase and Vps34 lipid kinase are two key autophagy regulators that are critical for autophagosome biogenesis. However, it isn't fully understood how ULK1 regulates Vps34, especially in the context of disease. Polyglutamine expansion in huntingtin (Htt) causes aberrant accumulation of the aggregated protein and disrupts various cellular pathways including autophagy, a lysosomal degradation pathway, underlying the pathogenesis of Huntington's disease (HD)...
December 9, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27916455/phosphodiesterase-10a-inhibition-improves-cortico-basal-ganglia-function-in-huntington-s-disease-models
#7
Vahri Beaumont, Sheng Zhong, Hai Lin, WenJin Xu, Amyaouch Bradaia, Esther Steidl, Melanie Gleyzes, Kristian Wadel, Bruno Buisson, Fernando E Padovan-Neto, Shreaya Chakroborty, Karen M Ward, John F Harms, Jose Beltran, Mei Kwan, Afshin Ghavami, Jenny Häggkvist, Miklós Tóth, Christer Halldin, Andrea Varrone, Christoph Schaab, J Nikolaj Dybowski, Sarah Elschenbroich, Kimmo Lehtimäki, Taneli Heikkinen, Larry Park, James Rosinski, Ladislav Mrzljak, Daniel Lavery, Anthony R West, Christopher J Schmidt, Margaret M Zaleska, Ignacio Munoz-Sanjuan
Huntington's disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models, and PDE10 loss may represent a homeostatic adaptation to maintain signaling...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27913290/early-and-brain-region-specific-decrease-of-de-novo-cholesterol-biosynthesis-in-huntington-s-disease-a-cross-validation-study-in-q175-knock-in-mice
#8
Mahalakshmi Shankaran, Eleonora Di Paolo, Valerio Leoni, Claudio Caccia, Costanza Ferrari Bardile, Hussein Mohammed, Stefano Di Donato, Seung Kwak, Deanna Marchionini, Scott Turner, Elena Cattaneo, Marta Valenza
Cholesterol precursors and cholesterol levels are reduced in brain regions of Huntington's disease (HD) mice. Here we quantified the rate of in vivo de novo cholesterol biosynthesis in the HD brain. Samples from different brain regions and blood of the heterozygous knock-in mouse model carrying 175 CAG repeats (Q175) at different phenotypic stages were processed independently by two research units to quantify cholesterol synthesis rate by (2)H2O labeling and measure the concentrations of lathosterol, cholesterol and its brain-specific cholesterol catabolite 24-hydroxy-cholesterol (24OHC) by isotope dilution mass spectrometry...
February 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27899419/progressive-cl-channel-defects-reveal-disrupted-skeletal-muscle-maturation-in-r6-2-huntington-s-mice
#9
Daniel R Miranda, Monica Wong, Shannon H Romer, Cynthia McKee, Gabriela Garza-Vasquez, Alyssa C Medina, Volker Bahn, Andrew D Steele, Robert J Talmadge, Andrew A Voss
Huntington's disease (HD) patients suffer from progressive and debilitating motor dysfunction. Previously, we discovered reduced skeletal muscle chloride channel (ClC-1) currents, inwardly rectifying potassium (Kir) channel currents, and membrane capacitance in R6/2 transgenic HD mice. The ClC-1 loss-of-function correlated with increased aberrant mRNA processing and decreased levels of full-length ClC-1 mRNA (Clcn1 gene). Physiologically, the resulting muscle hyperexcitability may help explain involuntary contractions of HD...
January 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/27646506/progressive-gene-dose-dependent-disruption-of-the-methamphetamine-sensitive-circadian-oscillator-driven-rhythms-in-a-knock-in-mouse-model-of-huntington-s-disease
#10
Koliane Ouk, Juliet Aungier, A Jennifer Morton
Huntington's disease (HD) is a progressive genetic neurodegenerative disorder characterised by motor and cognitive deficits, as well as sleep and circadian abnormalities. In the R6/2 mouse, a fragment model of HD, rest-activity rhythms controlled by the suprachiasmatic nucleus disintegrate completely by 4months of age. Rhythms driven by a second circadian oscillator, the methamphetamine-sensitive circadian oscillator (MASCO), are disrupted even earlier, and cannot be induced after 2months of age. Here, we studied the effect of the HD mutation on the expression of MASCO-driven rhythms in a more slowly developing, genetically relevant mouse model of HD, the Q175 'knock-in' mouse...
September 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27486903/white-adipose-tissue-browning-in-the-r6-2-mouse-model-of-huntington-s-disease
#11
Andrew C McCourt, Lovisa Jakobsson, Sara Larsson, Cecilia Holm, Sarah Piel, Eskil Elmér, Maria Björkqvist
Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1)...
2016: PloS One
https://www.readbyqxmd.com/read/27466197/pridopidine-activates-neuroprotective-pathways-impaired-in-huntington-disease
#12
Michal Geva, Rebecca Kusko, Holly Soares, Kevin D Fowler, Tal Birnberg, Steve Barash, Avia Merenlender -Wagner, Tania Fine, Andrew Lysaght, Brian Weiner, Yoonjeong Cha, Sarah Kolitz, Fadi Towfic, Aric Orbach, Ralph Laufer, Ben Zeskind, Iris Grossman, Michael R Hayden
Pridopidine has demonstrated improvement in Huntington Disease (HD) motor symptoms as measured by secondary endpoints in clinical trials. Originally described as a dopamine stabilizer, this mechanism is insufficient to explain the clinical and preclinical effects of pridopidine. This study therefore explored pridopidine's potential mechanisms of action. The effect of pridopidine versus sham treatment on genome-wide expression profiling in the rat striatum was analysed and compared to the pathological expression profile in Q175 knock-in (Q175 KI) vs Q25 WT mouse models...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27378694/an-enhanced-q175-knock-in-mouse-model-of-huntington-disease-with-higher-mutant-huntingtin-levels-and-accelerated-disease-phenotypes
#13
Amber L Southwell, Amy Smith-Dijak, Chris Kay, Marja Sepers, Erika B Villanueva, Matthew P Parsons, Yuanyun Xie, Lisa Anderson, Boguslaw Felczak, Sabine Waltl, Seunghyun Ko, Daphne Cheung, Louisa Dal Cengio, Ramy Slama, Eugenia Petoukhov, Lynn A Raymond, Michael R Hayden
Huntington disease (HD) model mice with heterozygous knock-in (KI) of an expanded CAG tract in exon 1 of the mouse huntingtin (Htt) gene homolog genetically recapitulate the mutation that causes HD, and might be favoured for preclinical studies. However, historically these mice have failed to phenotypically recapitulate the human disease. Thus, homozygous KI mice, which lack wildtype Htt, and are much less relevant to human HD, have been used. The zQ175 model was the first KI mouse to exhibit significant HD-like phenotypes when heterozygous...
September 1, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27356755/hotspot-mutations-delineating-diverse-mutational-signatures-and-biological-utilities-across-cancer-types
#14
Tenghui Chen, Zixing Wang, Wanding Zhou, Zechen Chong, Funda Meric-Bernstam, Gordon B Mills, Ken Chen
BACKGROUND: An important step towards personalizing cancer treatment is to integrate heterogeneous evidences to catalog mutational hotspots that are biologically and therapeutically relevant and thus represent where targeted therapy would likely be beneficial. However, existing methods do not sufficiently delineate varying functionality of individual mutations within the same genes. RESULTS: We observed a large discordancy of mutation rates across different mutation subtypes and tumor types, and nominated 702 hotspot mutations in 549 genes in the Catalog of Somatic Mutations in Cancer (COSMIC) by considering context specific mutation characteristics such as genes, cancer types, mutation rates, mutation subtypes and sequence contexts...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27147652/compromised-dopaminergic-encoding-of-reward-accompanying-suppressed-willingness-to-overcome-high-effort-costs-is-a-prominent-prodromal-characteristic-of-the-q175-mouse-model-of-huntington-s-disease
#15
Dan P Covey, Hannah M Dantrassy, Natalie E Zlebnik, Iness Gildish, Joseph F Cheer
UNLABELLED: Huntington's disease (HD) is a heritable neurodegenerative disorder caused by expansion of CAG (glutamine) repeats in the HTT gene. A prodromal stage characterized by psychiatric disturbances normally precedes primary motor symptoms and suppressed motivation represents one of the earliest and most common psychiatric symptoms. Although dopamine in the nucleus accumbens (NAc) critically regulates motivation and altered dopamine signaling is implicated in HD, the nature of dopaminergic deficits and contribution to symptoms in HD is poorly understood...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27147650/functional-indicators-of-glutamate-transport-in-single-striatal-astrocytes-and-the-influence-of-kir4-1-in-normal-and-huntington-mice
#16
Anton Dvorzhak, Tatyana Vagner, Knut Kirmse, Rosemarie Grantyn
UNLABELLED: This study evaluates single-cell indicators of glutamate transport in sulforhodamine 101-positive astrocytes of Q175 mice, a knock-in model of Huntington's disease (HD). Transport-related fluorescent ratio signals obtained with sodium-binding benzofuran isophtalate (SBFI) AM from unperturbed or voltage-clamped astrocytes and respective glutamate transporter currents (GTCs) were induced by photolytic or synaptic glutamate release and isolated pharmacologically. The HD-induced deficit ranged from -27% (GTC maximum at -100 mV in Ba(2+)) to -41% (sodium transients in astrocytes after loading SBFI-AM)...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26947127/the-p75-neurotrophin-receptor-augments-survival-signaling-in-the-striatum-of-pre-symptomatic-q175-wt-hd-mice
#17
A B Wehner, A M Milen, R L Albin, B A Pierchala
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a constellation of motor, cognitive, and psychiatric features. Striatal medium spiny neurons, one of the most affected populations, are dependent on brain-derived neurotrophic factor (BDNF) anterogradely transported from the cortex for proper function and survival. Recent studies suggest both receptors for BDNF, TrkB and p75 neurotrophin receptor (p75), are improperly regulated in the striata of HD patients and mouse models of HD...
June 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/26546830/pathological-gamma-oscillations-impaired-dopamine-release-synapse-loss-and-reduced-dynamic-range-of-unitary-glutamatergic-synaptic-transmission-in-the-striatum-of-hypokinetic-q175-huntington-mice
#18
T Rothe, M Deliano, A M Wójtowicz, A Dvorzhak, D Harnack, S Paul, T Vagner, I Melnick, H Stark, R Grantyn
Huntington's disease (HD) is a severe genetically inherited neurodegenerative disorder. Patients present with three principal phenotypes of motor symptoms: choreatic, hypokinetic-rigid and mixed. The Q175 mouse model of disease offers an opportunity to investigate the cellular basis of the hypokinetic-rigid form of HD. At the age of 1 year homozygote Q175 mice exhibited the following signs of hypokinesia: Reduced frequency of spontaneous movements on a precision balance at daytime (-55%), increased total time spent without movement in an open field (+42%), failures in the execution of unconditioned avoidance reactions (+32%), reduced ability for conditioned avoidance (-96%) and increased reaction times (+65%) in a shuttle box...
December 17, 2015: Neuroscience
https://www.readbyqxmd.com/read/25978848/abnormalities-in-the-tricarboxylic-acid-cycle-in-huntington-disease-and-in-a-huntington-disease-mouse-model
#19
Nima N Naseri, Hui Xu, Joseph Bonica, Jean Paul G Vonsattel, Etty P Cortes, Larry C Park, Jamshid Arjomand, Gary E Gibson
Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here, activities for these enzymes and select protein levels were measured in human postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA levels encoding for these enzymes were also measured in the Q175 mouse cortex...
June 2015: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/25673747/altered-excitatory-and-inhibitory-inputs-to-striatal-medium-sized-spiny-neurons-and-cortical-pyramidal-neurons-in-the-q175-mouse-model-of-huntington-s-disease
#20
Tim Indersmitten, Conny H Tran, Carlos Cepeda, Michael S Levine
The Q175 knockin mouse model of Huntington's disease (HD) carries a CAG trinucleotide expansion of the human mutant huntingtin allele in its native mouse genomic context and recapitulates the genotype more closely than transgenic models. In this study we examined the progression of changes in intrinsic membrane properties and excitatory and inhibitory synaptic transmission, using whole cell patch-clamp recordings of medium-sized spiny neurons (MSNs) in the dorsolateral striatum and cortical pyramidal neurons (CPNs) in layers 2/3 of the primary motor cortex in brain slices from heterozygous (Q175(+/-)) and homozygous (Q175(+/+)) mice...
April 1, 2015: Journal of Neurophysiology
keyword
keyword
70123
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"