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Transgenic Models of Behaviour

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https://www.readbyqxmd.com/read/28931441/tracking-progressive-pathological-and-functional-decline-in-the-rtg4510-mouse-model-of-tauopathy
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28857482/dopaminergic-and-behavioral-changes-in-a-loss-of-imprinting-model-of-cdkn1c
#5
Gráinne I McNamara, Brittany A Davis, Molly Browne, Trevor Humby, Jeffrey W Dalley, Jing Xia, Rosalind M John, Anthony R Isles
The imprinted gene Cdkn1c is expressed exclusively from the maternally inherited allele as a consequences of epigenetic regulation. Cdkn1c exemplifies many of the functional characteristics of imprinted genes, playing a role in fetal growth and placental development. However, Cdkn1c also plays an important role in the brain, being key to the appropriate proliferation and differentiation of midbrain dopaminergic neurons. Using a transgenic model (Cdkn1c(BACx1) ) with a two-fold elevation in Cdkn1c expression that mimics loss-of-imprinting, we show that increased expression of Cdkn1c in the brain gives rise to neurobiological and behavioural changes indicative of a functionally altered dopaminergic system...
August 31, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28854940/diesel-engine-exhaust-accelerates-plaque-formation-in-a-mouse-model-of-alzheimer-s-disease
#6
Maja Hullmann, Catrin Albrecht, Damiën van Berlo, Miriam E Gerlofs-Nijland, Tina Wahle, Agnes W Boots, Jean Krutmann, Flemming R Cassee, Thomas A Bayer, Roel P F Schins
BACKGROUND: Increasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer's Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0...
August 30, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28821829/neuromodulatory-circuit-effects-on-drosophila-feeding-behaviour-and-metabolism
#7
Anders Eriksson, Marlena Raczkowska, Rapeechai Navawongse, Deepak Choudhury, James C Stewart, Yi Ling Tang, Zhiping Wang, Adam Claridge-Chang
Animals have evolved to maintain homeostasis in a changing external environment by adapting their internal metabolism and feeding behaviour. Metabolism and behaviour are coordinated by neuromodulation; a number of the implicated neuromodulatory systems are homologous between mammals and the vinegar fly, an important neurogenetic model. We investigated whether silencing fly neuromodulatory networks would elicit coordinated changes in feeding, behavioural activity and metabolism. We employed transgenic lines that allowed us to inhibit broad cellular sets of the dopaminergic, serotonergic, octopaminergic, tyraminergic and neuropeptide F systems...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797124/preclinical-development-of-a-vaccine-against-oligomeric-alpha-synuclein-based-on-virus-like-particles
#8
Marika Doucet, Aadil El-Turabi, Franziska Zabel, Benjamin H M Hunn, Nora Bengoa-Vergniory, Milena Cioroch, Mauricio Ramm, Amy M Smith, Ariane Cruz Gomes, Gustavo Cabral de Miranda, Richard Wade-Martins, Martin F Bachmann
Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies...
2017: PloS One
https://www.readbyqxmd.com/read/28752194/from-engineering-to-editing-the-rat-genome
#9
Stephen Meek, Tomoji Mashimo, Tom Burdon
Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are now the mainstay of research on hypertension, obesity and neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J Hered 52(6):275-278, 1961)...
July 27, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28693862/behavioural-inflexibility-in-a-comorbid-rat-model-of-striatal-ischemic-injury-and-mutant-happ-overexpression
#10
Alexander Levit, Aaron M Regis, Jessica R Garabon, Seung-Hun Oh, Sagar J Desai, Nagalingam Rajakumar, Vladimir Hachinski, Yuksel Agca, Cansu Agca, Shawn N Whitehead, Brian L Allman
Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease...
July 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28623605/cathepsin-c-aggravates-neuroinflammation-involved-in-disturbances-of-behaviour-and-neurochemistry-in-acute-and-chronic-stress-induced-murine-model-of-depression
#11
Yanli Zhang, Kai Fan, Yanna Liu, Gang Liu, Xiaohan Yang, Jianmei Ma
Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28613391/evaluation-of-five-diffeomorphic-image-registration-algorithms-for-mouse-brain-magnetic-resonance-microscopy
#12
Zhenrong Fu, Lan Lin, Miao Tian, Jingxuan Wang, Baiwen Zhang, Pingping Chu, Shaowu Li, Muhammad Mohsin Pathan, Yulin Deng, Shuicai Wu
The development of genetically engineered mouse models for neuronal diseases and behavioural disorders have generated a growing need for small animal imaging. High-resolution magnetic resonance microscopy (MRM) provides powerful capabilities for noninvasive studies of mouse brains, while avoiding some limits associated with the histological procedures. Quantitative comparison of structural images is a critical step in brain imaging analysis, which highly relies on the performance of image registration techniques...
June 14, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28596596/optical-mapping-of-neuronal-activity-during-seizures-in-zebrafish
#13
L Turrini, C Fornetto, G Marchetto, M C Müllenbroich, N Tiso, A Vettori, F Resta, A Masi, G Mannaioni, F S Pavone, F Vanzi
Mapping neuronal activity during the onset and propagation of epileptic seizures can provide a better understanding of the mechanisms underlying this pathology and improve our approaches to the development of new drugs. Recently, zebrafish has become an important model for studying epilepsy both in basic research and in drug discovery. Here, we employed a transgenic line with pan-neuronal expression of the genetically-encoded calcium indicator GCaMP6s to measure neuronal activity in zebrafish larvae during seizures induced by pentylenetretrazole (PTZ)...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28593819/voluntary-exercise-improves-cognitive-deficits-in-female-dominant-negative-disc1-transgenic-mouse-model-of-neuropsychiatric-disorders
#14
Hadar Segal-Gavish, Ran Barzilay, Ofri Rimoni, Daniel Offen
OBJECTIVES: Physical exercise has gained increasing interest as a treatment modality that improves prognosis in psychiatric patients. The disrupted in schizophrenia 1 (DISC1) gene is a candidate gene for major mental illness. In this study, we aimed to determine whether voluntary wheel running can improve cognitive deficits of dominant-negative DISC1 transgenic mice (DN-DISC1). METHODS: DN-DISC1 and control mice (10-week-old male and female) were placed for 14 days in a cage with or without access to a running wheel...
June 8, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28520590/role-of-tyrosine-kinase-inhibitors-in-the-treatment-of-pituitary-tumours-from-bench-to-bedside
#15
Anat Ben-Shlomo, Odelia Cooper
PURPOSE OF REVIEW: Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease...
August 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28516241/innate-immunity-in-alzheimer-s-disease-the-relevance-of-animal-models
#16
REVIEW
Diana K Franco Bocanegra, James A R Nicoll, Delphine Boche
The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment...
May 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28501482/ciproxifan-improves-cholinergic-transmission-attenuates-neuroinflammation-and-oxidative-stress-but-does-not-reduce-amyloid-level-in-transgenic-mice
#17
Vasudevan Mani, Siti Murnirah Jaafar, Nur Syamimi Mohd Azahan, Kalavathy Ramasamy, Siong Meng Lim, Long Chiau Ming, Abu Bakar Abdul Majeed
AIM: The present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit β-amyloid (Aβ)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND METHODS: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Aβ25-35 - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days and behaviour was assessed using the radial arm maze (RAM)...
July 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28484229/characterizing-microglia-activation-a-spatial-statistics-approach-to-maximize-information-extraction
#18
Benjamin M Davis, Manual Salinas-Navarro, M Francesca Cordeiro, Lieve Moons, Lies De Groef
Microglia play an important role in the pathology of CNS disorders, however, there remains significant uncertainty about the neuroprotective/degenerative role of these cells due to a lack of techniques to adequately assess their complex behaviour in response to injury. Advancing microscopy techniques, transgenic lines and well-characterized molecular markers, have made histological assessment of microglia populations more accessible. However, there is a distinct lack of tools to adequately extract information from these images to fully characterise microglia behaviour...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28480797/tnf%C3%AE-depleting-therapy-improves-fertility-and-animal-welfare-in-tnf%C3%AE-driven-transgenic-models-of-polyarthritis-when-administered-in-their-routine-breeding
#19
Amy J Naylor, Guillaume Desanti, Atif N Saghir, Rowan S Hardy
Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNF(ΔARE) mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy 'infliximab' might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNF(ΔARE) males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection...
January 1, 2017: Laboratory Animals
https://www.readbyqxmd.com/read/28416454/e1a-is-an-exogenous-in%C3%A2-vivo-tumour-suppressor
#20
Francisco J Cimas, Juan L Callejas-Valera, Dolores C García-Olmo, Javier Hernández-Losa, Pedro Melgar-Rojas, María J Ruiz-Hidalgo, Raquel Pascual-Serra, Marta Ortega-Muelas, Olga Roche, Pilar Marcos, Elena Garcia-Gil, Diego M Fernandez-Aroca, Santiago Ramón Y Cajal, J Silvio Gutkind, Ricardo Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent)...
July 28, 2017: Cancer Letters
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