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Transgenic Models of Behaviour

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https://www.readbyqxmd.com/read/29778627/impaired-spatial-processing-in-a-mouse-model-of-fragile-x-syndrome
#1
Mohamed Ghilan, Luis Bettio, Athena Noonan, Patricia S Brocardo, Joana Gil-Mohapel, Brian R Christie
Fragile X syndrome (FXS) is the most common form of inherited intellectual impairment. The Fmr1-/y mouse model has been previously shown to have deficits in context discrimination tasks but not in the elevated plus-maze. To further characterize this FXS mouse model and determine whether hippocampal-mediated behaviours are affected in these mice, dentate gyrus (DG)-dependent spatial processing and Cornu Ammonis 1 (CA1)-dependent temporal order discrimination tasks were evaluated. In agreement with previous findings of long-term potentiation deficits in the DG of this transgenic model of FXS, the results reported here demonstrate that Fmr1-/y mice perform poorly in the DG-dependent metric change spatial processing task...
May 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29736183/universality-of-clone-dynamics-during-tissue-development
#2
Steffen Rulands, Fabienne Lescroart, Samira Chabab, Christopher J Hindley, Nicole Prior, Magdalena K Sznurkowska, Meritxell Huch, Anna Philpott, Cedric Blanpain, Benjamin D Simons
The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes...
May 2018: Nature Physics
https://www.readbyqxmd.com/read/29683360/hydrogen-rich-water-improves-cognitive-impairment-gender-dependently-in-app-ps1-mice-without-affecting-a%C3%AE-clearance
#3
Chen Hou, Yunhua Peng, Chuan Qin, Fan Fan, Jiankang Liu, Jiangang Long
Alzheimer's disease (AD) is characterised as a provoked inflammatory response and oxidative stress along with amyloid β peptide (Aβ) deposition and neurofibrillary tangles in the brain, and effective treatment is greatly needed. Molecular hydrogen, which has been proposed to be an antioxidant that selectively reduces reactive oxygen species, was found to exert beneficial effects in Aβ injection-induced cognitive dysfunction. However, whether and how hydrogen affects AD pathogenesis remains uninvestigated...
April 23, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29662090/optical-interrogation-of-neuronal-circuitry-in-zebrafish-using-genetically-encoded-voltage-indicators
#4
Hiroaki Miyazawa, Kanoko Okumura, Kanae Hiyoshi, Kazuhiro Maruyama, Hisaya Kakinuma, Ryunosuke Amo, Hitoshi Okamoto, Kyo Yamasu, Sachiko Tsuda
Optical measurement of membrane potentials enables fast, direct and simultaneous detection of membrane potentials from a population of neurons, providing a desirable approach for functional analysis of neuronal circuits. Here, we applied recently developed genetically encoded voltage indicators, ASAP1 (Accelerated Sensor of Action Potentials 1) and QuasAr2 (Quality superior to Arch 2), to zebrafish, an ideal model system for studying neurogenesis. To achieve this, we established transgenic lines which express the voltage sensors, and showed that ASAP1 is expressed in zebrafish neurons...
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29651780/sub-cellular-markers-highlight-intracellular-dynamics-of-membrane-proteins-in-response-to-abiotic-treatments-in-rice
#5
Thi Thu Huyen Chu, Thi Giang Hoang, Duy Chi Trinh, Charlotte Bureau, Donaldo Meynard, Aurore Vernet, Mathieu Ingouff, Nang Vinh Do, Christophe Périn, Emmanuel Guiderdoni, Pascal Gantet, Christophe Maurel, Doan-Trung Luu
BACKGROUND: Cell biology approach using membrane protein markers tagged with fluorescent proteins highlights the dynamic behaviour of plant cell membranes, not only in the standard but also in changing environmental conditions. In the past, this strategy has been extensively developed in plant models such as Arabidopsis. RESULTS: Here, we generated a set of transgenic lines expressing membrane protein markers to extend this approach to rice, one of the most cultivated crop in the world and an emerging plant model...
April 12, 2018: Rice
https://www.readbyqxmd.com/read/29559337/schizophrenia-relevant-behaviours-of-female-mice-overexpressing-neuregulin-1-type-iii
#6
Juan C Olaya, Carrie L Heusner, Mitsuyuki Matsumoto, Cynthia Shannon Weickert, Tim Karl
Elevated levels of the type III (III) isoforms of neuregulin 1 (NRG1) have been observed in the brains of schizophrenia patients that carry NRG1 HapICE risk alleles, which is thought to contribute to the aetiology of the disease. We generated transgenic mice with forebrain driven Nrg1 III overexpression (Nrg1 III tg) and previously found that male heterozygous Nrg1 type III tg mice exhibit several schizophrenia-relevant behaviours including social and cognitive deficits as well as impaired sensorimotor gating...
March 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29528390/expression-of-c9orf72-related-dipeptides-impairs-motor-function-in-a-vertebrate-model
#7
Amrutha Swaminathan, Marilou Bouffard, Meijiang Liao, Sarah Ryan, Janis Bennion Callister, Stuart M Pickering-Brown, Gary Alan Barclay Armstrong, Pierre Drapeau
Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the underlying disease mechanism including loss of function by haploinsufficiency, toxicity arising as a result of RNA or dipeptide repeats (DPRs). Five different DPRs are produced by repeat-associated non-ATG-initiated translation of the G4C2 repeats...
May 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29426354/lentivirus-mediated-expression-of-human-secreted-amyloid-precursor-protein-alpha-prevents-development-of-memory-and-plasticity-deficits-in-a-mouse-model-of-alzheimer-s-disease
#8
Valerie T Y Tan, Bruce G Mockett, Shane M Ohline, Karen D Parfitt, Hollie E Wicky, Katie Peppercorn, Lucia Schoderboeck, Mohamad Fairuz Bin Yahaya, Warren P Tate, Stephanie M Hughes, Wickliffe C Abraham
Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αβ, sAPPα has many neuroprotective and neurotrophic properties. Increasing sAPPα levels has the potential to serve as a therapeutic treatment that mitigates the effects of Aβ and rescue cognitive function...
February 9, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29425692/a-rapidly-acquired-foraging-based-working-memory-task-sensitive-to-hippocampal-lesions-reveals-age-dependent-and-age-independent-behavioural-changes-in-a-mouse-model-of-amyloid-pathology
#9
Charles Evans, Martha Hvoslef-Eide, Rhian Thomas, Emma Kidd, Mark A Good
Three experiments examined the ability of mice to forage efficiently for liquid rewards in pots located in an open field arena. Search behaviour was unconstrained other than by the walls of the arena. All mice acquired the task within 4 days of training, with one trial per day. Experiment 1 tested the hypothesis that hippocampal lesions would disrupt foraging behaviour using extramaze cues. Mice with hippocampal lesions showed normal latency to initiate foraging and to complete the task relative to sham-operated mice...
March 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29405035/protective-effects-of-long-term-lithium-administration-in-a-slowly-progressive-sma-mouse-model
#10
Francesca Biagioni, Michela Ferrucci, Larisa Ryskalin, Federica Fulceri, Gloria Lazzeri, Maria Teresa Calierno, Carla L Busceti, Riccardo Ruffoli, Francesco Fornai
In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course...
December 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29274752/chronic-paroxetine-treatment-prevents-disruption-of-methamphetamine-sensitive-circadian-oscillator-in-a-transgenic-mouse-model-of-huntington-s-disease
#11
Koliane Ouk, Juliet Aungier, Marc Cuesta, A Jennifer Morton
Circadian abnormalities seen in Huntington's disease (HD) patients are recapitulated in several HD transgenic mouse models. In mice, alongside the master clock located in the suprachiasmatic nucleus (SCN), two other oscillators may influence circadian behaviour. These are the food-entrainable oscillator (FEO) and the methamphetamine-sensitive circadian oscillator (MASCO). SCN- and MASCO- (but not FEO-) driven rhythms are progressively disrupted in the R6/2 mouse model of HD. MASCO-driven rhythms are induced by chronic treatment with low dose of methamphetamine and characterised by an increase in period length to greater than 24 h...
March 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29170392/larval-dispersal-of-spodoptera-frugiperda-strains-on-bt-cotton-a-model-for-understanding-resistance-evolution-and-consequences-for-its-management
#12
José B Malaquias, Wesley A C Godoy, Adriano G Garcia, Francisco de S Ramalho, Celso Omoto
High dispersal of Lepidoptera larvae between non-Bt and Bt cotton plants can favour the evolution of insect resistance; however, information on host acceptance of neonates in tropical transgenic crops is scarce. Therefore, the purposes of this study were as follows: (i) to investigate the feeding behaviour of susceptible and Cry1F-resistant strains of Spodoptera frugiperda (J.E. Smith) on Bt and non-Bt cotton (Gossypium hirsutum L.) varieties and (ii) to understand the possible effects of cotton field contamination on the dispersal and infestation capacity of S...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097807/tdp-43-accelerates-age-dependent-degeneration-of-interneurons
#13
Hitomi Tsuiji, Ikuyo Inoue, Mari Takeuchi, Asako Furuya, Yuko Yamakage, Seiji Watanabe, Masato Koike, Mitsuharu Hattori, Koji Yamanaka
TDP-43 is an RNA-binding protein important for many aspects of RNA metabolism. Abnormal accumulation of TDP-43 in the cytoplasm of affected neurons is a pathological hallmark of the neurodegenerative diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Several transgenic mouse models have been generated that recapitulate defects in TDP-43 accumulation, thus causing neurodegeneration and behavioural impairments. While aging is the key risk factor for neurodegenerative diseases, the specific effect of aging on phenotypes in TDP-43 transgenic mice has not been investigated...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#14
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies...
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28969319/effects-of-propofol-and-surgery-on-neuropathology-and-cognition-in-the-3xtgad-alzheimer-transgenic-mouse-model
#15
F Mardini, J X Tang, J C Li, M J Arroliga, R G Eckenhoff, M F Eckenhoff
Background: Previous work suggests that anaesthesia and surgery amplify the pathology and cognitive impairment of animals made vulnerable via age or specific transgenes. We hypothesized that surgery under propofol anaesthesia, a widely used i.v. general anaesthetic, has minimal delayed cognitive and neuroinflammatory sequelae in a vulnerable mouse transgenic model. Methods: We conducted caecal ligation and excision surgery in cognitively presymptomatic (11-month-old) 3xTgAD mice under i...
September 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28956337/role-of-phosphodiesterases-in-huntington-s-disease
#16
REVIEW
Francesca R Fusco, Emanuela Paldino
Huntington's disease (HD) is an autosomal-dominant rare inherited neurodegenerative disease characterized by a wide variety of symptoms encompassing movement, cognition and behaviour. The cause of the disease is a genetic mutation in the huntingtin protein. The mutation leads to an unstable CAG expansion, translated into a polyglutamine domain within the disease protein. Indeed, huntingtin has a CAG/polyglutamine expansion in the range of 6-39 units in normal individuals, whereas it reaches 39-180 units in HD patients...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28931441/tracking-progressive-pathological-and-functional-decline-in-the-rtg4510-mouse-model-of-tauopathy
#17
Thomas Blackmore, Soraya Meftah, Tracey Karen Murray, Peter James Craig, Anthony Blockeel, Keith Phillips, Brian Eastwood, Michael J O'Neill, Hugh Marston, Zeshan Ahmed, Gary Gilmour, Francois Gastambide
BACKGROUND: The choice and appropriate use of animal models in drug discovery for Alzheimer's disease (AD) is pivotal to successful clinical translation of novel therapeutics, yet true alignment of research is challenging. Current models do not fully recapitulate the human disease, and even exhibit various degrees of regional pathological burden and diverse functional alterations. Given this, relevant pathological and functional endpoints must be determined on a model-by-model basis. The present work explores the rTg4510 mouse model of tauopathy as a case study to define best practices for the selection and validation of cognitive and functional endpoints for the purposes of pre-clinical AD drug discovery...
September 20, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899017/cortical-functional-hyperconnectivity-in-a-mouse-model-of-depression-and-selective-network-effects-of-ketamine
#18
Alexander McGirr, Jeffrey LeDue, Allen W Chan, Yicheng Xie, Timothy H Murphy
See Huang and Liston (doi:10.1093/awx166) for a scientific commentary on this article.Human depression is associated with glutamatergic dysfunction and alterations in resting state network activity. However, the indirect nature of human in vivo glutamate and activity assessments obscures mechanistic details. Using the chronic social defeat mouse model of depression, we determine how mesoscale glutamatergic networks are altered after chronic stress, and in response to the rapid acting antidepressant, ketamine...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28887197/reduction-in-open-field-activity-in-the-absence-of-memory-deficits-in-the-app-nl-g-f-knock-in-mouse-model-of-alzheimer-s-disease
#19
Lauren S Whyte, Kim M Hemsley, Adeline A Lau, Sofia Hassiotis, Takashi Saito, Takaomi C Saido, John J Hopwood, Timothy J Sargeant
The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App(NL-F) and App(NL-G-F) mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App(NL-G-F/NL-G-F) (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App(NL-G-F/NL-G-F) and wild-type mice...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28880417/neuropathology-and-behavioural-features-of-transgenic-murine-models-of-alzheimer-s-disease
#20
Kamar E Ameen-Ali, Stephen B Wharton, Julie E Simpson, Paul R Heath, Paul Sharp, Jason Berwick
Our understanding of the underlying biology of Alzheimer's disease (AD) has been steadily progressing; however, this is yet to translate into a successful treatment in humans. The use of transgenic mouse models has helped to develop our understanding of AD, not only in terms of disease pathology, but also with the associated cognitive impairments typical of AD. Plaques and neurofibrillary tangles are often amongst the last pathological changes in AD mouse models, after neuronal loss and gliosis. There is a general consensus that successful treatments need to be applied before the onset of these pathologies and associated cognitive symptoms...
September 7, 2017: Neuropathology and Applied Neurobiology
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