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Michael Bader - One of the best experts on this subject based on the ideXlab platform.
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Characterization of a novel Transgenic Rat model for imaging brain vascular dynamics in vivo using confocal endomicroscopy (686.27)
The FASEB Journal, 2014Co-Authors: Dmitry Mayorov, Michael Bader, Natalia Alenina, Eva V. L. Roloff, Anja G. Teschemacher, Julian F. R. Paton, Sergey KasparovAbstract:We evaluated the feasibility of imaging brain vasculature in a Transgenic Rat model (L7543) which expressed a construct carrying the eGFP under the control of CAG promoter (Popova et al., Transgen. Res. 2008) using fiber endomicroscopy (CellVizio, Mauna Kea Technologies). eGFP expression were first evaluated in cortical and brainstem slices from L7543 Rat using confocal microscopy (Leica SP5). Expression of eGFP in the cortex and brainstem was largely restricted to endothelial cells, although astrocytes in younger Rats (up to P35) were also fluorescent. Next, the brainstem and cortex were imaged, without a contrasting agent, in anaesthetized P21-P40 Rats using a fiber probe-based confocal laser endomicroscopy. Pial microvessels of the ventral or dorsal brainstem, or cortex were imaged using S-1500 and Mini-Z probes (1.5 and 0.94 mm tip diameter, respectively). The vascular contractility was visualized after application of a thromboxane agonist U46619 and sodium nitroprusside. Arterioles and veins were ide...
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Inducible Transgenic Rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
PloS one, 2009Co-Authors: Katarina Kotnik, Elena Popova, Mihail Todiras, Marcelo A. Mori, Natalia Alenina, Jost Seibler, Michael BaderAbstract:The Rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce Transgenic knockdown Rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR). Doxycycline (DOX) treatment of the resulting Transgenic Rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquitous inhibition of IR expression and signalling. We could neither detect an interferon response nor disturbances in microRNA processing after DOX treatment excluding toxic effects of shRNA expression. Low dose DOX treatment induced a chronic state of diabetes mellitus. In conclusion, we have developed a technology which allows the specific, inducible, and reversible suppression of any gene of interest in the Rat. Our first Transgenic Rat line geneRated with this method represents an inducible model for diabetes mellitus.
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GeneRation and characterization of a GFP Transgenic Rat line for embryological research.
Transgenic research, 2008Co-Authors: Elena Popova, Michael Bader, Brit Rentzsch, Alexander KrivokharchenkoAbstract:Model organisms expressing fluorescent proteins are important tools for research. The present study was performed to geneRate and characterize a new line of green fluorescent protein (GFP) Transgenic Rats for use as a model in experimental embryological research. We injected a GFP expression vector into 135 zygotes of the Sprague-Dawley (SD) Rat strain. Embryo transfer of 103 surviving embryos resulted in the production of 35 offspring (33.9%) and two of them were Transgenic (5.7%). Two Transgenic Rat lines that ubiquitously express GFP under the control of the cytomegalovirus-enhancer/β-actin (CAGGS) promoter were geneRated by breeding. We studied the main embryological parameters of one these GFP Transgenic lines. Homozygous GFP-Transgenic females have the same ovulation and superovulation Rates as wild type (WT) females. Transgenic embryos reached blastocyst stage in vitro and developed in vivo after embryo transfer without decrease in their developmental ability compared to the control group. The genotype of the parents determined the onset of GFP expression in preimplantation embryos. When the GFP gene is derived from the Transgenic female parent, fluorescence was detected in oocytes and in embryos of all further stages of development. When the GFP gene is inherited by the Transgenic male parent, GFP was only expressed from the blastocyst stage on. GFP-Transgenic Rats represent a valuable tool to mark embryos for many embryological studies such as transgenesis, gene expression patterns during early development, embryo aggregation for analysis of the distribution of cells in chimeric embryos and nuclear transfer to confirm the origin of the cloned offspring.
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A Transgenic Rat expressing human APP with the Swedish Alzheimer's disease mutation.
Biochemical and biophysical research communications, 2007Co-Authors: Ronnie Folkesson, Michael Bader, Ursula Ganten, Ewa Kloskowska, Tatjana Nilsson, Katarzyna Malkiewicz, Detlev Ganten, Elena Popova, Nenad Bogdanovic, Bengt WinbladAbstract:In recent years, Transgenic mice have become valuable tools for studying mechanisms of Alzheimer's disease (AD). With the aim of developing an animal model better for memory and neurobehavioural testing, we have geneRated a Transgenic Rat model of AD. These animals express human amyloid precursor protein (APP) containing the Swedish AD mutation. The highest level of expression in the brain is found in the cortex, hippocampus, and cerebellum. Starting after the age of 15 months, the Rats show increased tau phosphorylation and extracellular Abeta staining. The Abeta is found predominantly in cerebrovascular blood vessels with very rare diffuse plaques. We believe that crossing these animals with mutant PS1 Transgenic Rats will result in acceleRated plaque formation similar to that seen in Transgenic mice.
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Brain angiotensin and anxiety-related behavior: the Transgenic Rat TGR(ASrAOGEN)680.
Brain Research, 2005Co-Authors: Jörg-peter Voigt, Michael Bader, André Rex, Heide Hörtnagl, Lil Van Hove, Heidrun FinkAbstract:The Transgenic Rat TGR(ASrAOGEN)680, characterized by a transgene-producing antisense RNA against angiotensinogen in the brain, provides an opportunity to study the behavioral effects of angiotensin. While exposed to the elevated plus-maze (EPM) and the light/dark box, TGR(ASrAOGEN)680 Rats showed more signs of anxiety compared to parental Sprague-Dawley (SD) Rats. In the EPM, they made fewer entries into the open arms, spent less time there and more time on the closed arms. Head dips were reduced and U-turns were increased. In the light/dark box, the latency to the first re-entry into the light compartment was higher in TGR(ASrAOGEN)680. They displayed more SAP out from the dark and a reduced number of transitions between the two compartments. In the social interaction test, active social contacts were reduced, further suggesting an anxious phenotype. Although there was no Transgenic effect on distance traveled in the open field, the more anxious TGR(ASrAOGEN)680 spent less time in the inner zone. Self-grooming was increased in TGR(ASrAOGEN)680 during exposure to the EPM and the open field, but was decreased in the social interaction test. In TGR(ASrAOGEN)680, tissue content of 5-HT and its metabolite 5-HIAA was lower in the hippocampus, frontal, and parietal cortex. HIAA and 5-HIAA/5-HT Ratios were reduced in the hypothalamus, striatum, and septum. In the open field, the anxiogenic effect of the 5-HT2C/1B receptor agonist mCPP (0.5-1 mg/kg IP) was more pronounced in TGR(ASrAOGEN)680. The data suggest an anxious phenotype in Rats with low brain angiotensinogen, possibly related to secondary dysfunctions of the brain serotonergic system.
Tetsuya Terasaki - One of the best experts on this subject based on the ideXlab platform.
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Vascular EndotheliumSelective Gene Induction by Tie2 Promoter/Enhancer in the Brain and Retina of a Transgenic Rat
Pharmaceutical research, 2005Co-Authors: Sumio Ohtsuki, Naoko Kamiya, Satoko Hori, Tetsuya TerasakiAbstract:Purpose To produce a Transgenic Rat harboring the Tie2 promoter/enhancer linked green fluorescence protein (GFP) gene and investigate the blood-brain barrier (BBB)- and inner blood-retinal barrier (iBRB)-selective GFP expression in the brain and retina.
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Vascular EndotheliumSelective Gene Induction by Tie2 Promoter/Enhancer in the Brain and Retina of a Transgenic Rat
Pharmaceutical Research, 2005Co-Authors: Sumio Ohtsuki, Naoko Kamiya, Satoko Hori, Tetsuya TerasakiAbstract:Purpose To produce a Transgenic Rat harboring the Tie2 promoter/enhancer linked green fluorescence protein (GFP) gene and investigate the blood-brain barrier (BBB)- and inner blood-retinal barrier (iBRB)-selective GFP expression in the brain and retina. Methods Transgenic Rats were produced by the microinjection of mouse Tie2/GFP gene into fertilized oocytes of Wistar Rats. The expression of GFP was observed in tissue slices by confocal microscopy. Results One of the obtained Transgenic lines showed intense GFP expression in vascular endothelial cells throughout the brain. After double immunostaining with glucose transporter 1, the GFP was found to be localized in the cytoplasmic compartment of brain capillary endothelial cells. In contrast, no fluorescence was observed in neural cells. In the retina of Transgenic Rats, intense GFP expression was detected in retinal capillary endothelial cells. No fluorescence was detected in other cells. In kidney and liver, GFP expression was detected in vascular endothelial cells, whereas the expressed region was limited. Conclusions Mouse Tie2 promoter/enhancer has the ability to induce gene expression selectively in vascular endothelial cells in the brain and retina of Transgenic Rats.
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Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a Transgenic Rat.
Experimental eye research, 2001Co-Authors: Ken-ichi Hosoya, Masatsugu Ueda, Sumio Ohtsuki, Masatoshi Tomi, Hitomi Takanaga, Nobuaki Yanai, Masuo Obinata, Tetsuya TerasakiAbstract:Abstract The objective of this study was to establish and characterize a retinal capillary endothelial cell line (TR-iBRB) from a newly developed Transgenic Rat harboring the tempeRature-sensitive simian virus 40 (SV 40) large T-antigen gene (Tg Rat). Retinal capillary endothelial cells were isolated from a Tg Rat and cultured in collagen-coated dishes at 37°C for a period of 48 hr. Cells were subsequently cultured at 33°C to activate the large T-antigen. At the third passage, cells were cloned by colony formation and isolated from other cells. Nine immortalized cell lines of retinal capillary endothelial cells (TR-iBRB1 ∼ 9) were obtained from a Tg Rat. These cell lines had a spindle-fiber shape morphology, expressed the typical endothelial marker, von Willebrand factor, and internalized acetylated-low density lipoprotein. Moreover, vascular endothelial growth factor (VEGF) receptor-2 was expressed in TR-iBRBs. TR-iBRBs expressed a large T-antigen and grew well at 33°C with a doubling time of 19–21 hr. In contrast, cells did not grow at 37 and 39°C due to the reduced expression of large T-antigen, supporting tempeRature-dependent cell growth. TR-iBRBs expressed GLUT1 and exhibited 3- O -methyl- D -glucose (3-OMG) uptake activity. This 3-OMG uptake was saturable with a Michaelis–Menten constant of 5.56 ± 0.51 m M and a maximum uptake Rate of 45.3 ± 2.6 nmol min−1 mg protein−1. P-Glycoprotein, with a molecular weight of ∼180 KDa, was expressed in TR-iBRBs. In addition, mdr 1a, mdr 1b andmdr 2 were detected in TR-iBRB2 using RT-PCR. In conclusion, conditionally immortalized retinal capillary endothelial cell lines were established from a Transgenic Rat harboring the tempeRature-sensitive SV 40 large T-antigen gene and these lines were shown to exhibit the properties of retinal capillary endothelial cells.
Sumio Ohtsuki - One of the best experts on this subject based on the ideXlab platform.
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Vascular EndotheliumSelective Gene Induction by Tie2 Promoter/Enhancer in the Brain and Retina of a Transgenic Rat
Pharmaceutical research, 2005Co-Authors: Sumio Ohtsuki, Naoko Kamiya, Satoko Hori, Tetsuya TerasakiAbstract:Purpose To produce a Transgenic Rat harboring the Tie2 promoter/enhancer linked green fluorescence protein (GFP) gene and investigate the blood-brain barrier (BBB)- and inner blood-retinal barrier (iBRB)-selective GFP expression in the brain and retina.
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Vascular EndotheliumSelective Gene Induction by Tie2 Promoter/Enhancer in the Brain and Retina of a Transgenic Rat
Pharmaceutical Research, 2005Co-Authors: Sumio Ohtsuki, Naoko Kamiya, Satoko Hori, Tetsuya TerasakiAbstract:Purpose To produce a Transgenic Rat harboring the Tie2 promoter/enhancer linked green fluorescence protein (GFP) gene and investigate the blood-brain barrier (BBB)- and inner blood-retinal barrier (iBRB)-selective GFP expression in the brain and retina. Methods Transgenic Rats were produced by the microinjection of mouse Tie2/GFP gene into fertilized oocytes of Wistar Rats. The expression of GFP was observed in tissue slices by confocal microscopy. Results One of the obtained Transgenic lines showed intense GFP expression in vascular endothelial cells throughout the brain. After double immunostaining with glucose transporter 1, the GFP was found to be localized in the cytoplasmic compartment of brain capillary endothelial cells. In contrast, no fluorescence was observed in neural cells. In the retina of Transgenic Rats, intense GFP expression was detected in retinal capillary endothelial cells. No fluorescence was detected in other cells. In kidney and liver, GFP expression was detected in vascular endothelial cells, whereas the expressed region was limited. Conclusions Mouse Tie2 promoter/enhancer has the ability to induce gene expression selectively in vascular endothelial cells in the brain and retina of Transgenic Rats.
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Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a Transgenic Rat.
Experimental eye research, 2001Co-Authors: Ken-ichi Hosoya, Masatsugu Ueda, Sumio Ohtsuki, Masatoshi Tomi, Hitomi Takanaga, Nobuaki Yanai, Masuo Obinata, Tetsuya TerasakiAbstract:Abstract The objective of this study was to establish and characterize a retinal capillary endothelial cell line (TR-iBRB) from a newly developed Transgenic Rat harboring the tempeRature-sensitive simian virus 40 (SV 40) large T-antigen gene (Tg Rat). Retinal capillary endothelial cells were isolated from a Tg Rat and cultured in collagen-coated dishes at 37°C for a period of 48 hr. Cells were subsequently cultured at 33°C to activate the large T-antigen. At the third passage, cells were cloned by colony formation and isolated from other cells. Nine immortalized cell lines of retinal capillary endothelial cells (TR-iBRB1 ∼ 9) were obtained from a Tg Rat. These cell lines had a spindle-fiber shape morphology, expressed the typical endothelial marker, von Willebrand factor, and internalized acetylated-low density lipoprotein. Moreover, vascular endothelial growth factor (VEGF) receptor-2 was expressed in TR-iBRBs. TR-iBRBs expressed a large T-antigen and grew well at 33°C with a doubling time of 19–21 hr. In contrast, cells did not grow at 37 and 39°C due to the reduced expression of large T-antigen, supporting tempeRature-dependent cell growth. TR-iBRBs expressed GLUT1 and exhibited 3- O -methyl- D -glucose (3-OMG) uptake activity. This 3-OMG uptake was saturable with a Michaelis–Menten constant of 5.56 ± 0.51 m M and a maximum uptake Rate of 45.3 ± 2.6 nmol min−1 mg protein−1. P-Glycoprotein, with a molecular weight of ∼180 KDa, was expressed in TR-iBRBs. In addition, mdr 1a, mdr 1b andmdr 2 were detected in TR-iBRB2 using RT-PCR. In conclusion, conditionally immortalized retinal capillary endothelial cell lines were established from a Transgenic Rat harboring the tempeRature-sensitive SV 40 large T-antigen gene and these lines were shown to exhibit the properties of retinal capillary endothelial cells.
Detlev Ganten - One of the best experts on this subject based on the ideXlab platform.
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A Transgenic Rat expressing human APP with the Swedish Alzheimer's disease mutation.
Biochemical and biophysical research communications, 2007Co-Authors: Ronnie Folkesson, Michael Bader, Ursula Ganten, Ewa Kloskowska, Tatjana Nilsson, Katarzyna Malkiewicz, Detlev Ganten, Elena Popova, Nenad Bogdanovic, Bengt WinbladAbstract:In recent years, Transgenic mice have become valuable tools for studying mechanisms of Alzheimer's disease (AD). With the aim of developing an animal model better for memory and neurobehavioural testing, we have geneRated a Transgenic Rat model of AD. These animals express human amyloid precursor protein (APP) containing the Swedish AD mutation. The highest level of expression in the brain is found in the cortex, hippocampus, and cerebellum. Starting after the age of 15 months, the Rats show increased tau phosphorylation and extracellular Abeta staining. The Abeta is found predominantly in cerebrovascular blood vessels with very rare diffuse plaques. We believe that crossing these animals with mutant PS1 Transgenic Rats will result in acceleRated plaque formation similar to that seen in Transgenic mice.
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Efficiency of Transgenic Rat production is independent of transgene-construct and overnight embryo culture.
Theriogenology, 2004Co-Authors: Elena Popova, Detlev Ganten, Alexander Krivokharchenko, Michael BaderAbstract:The aim of the present work was to study factors affecting the efficiency of Transgenic technology in Rats. We investigated the possible effects of pronuclear microinjection of buffer or different DNA-constructs on survival and development of Rat zygotes in vitro and in vivo as well as the influence of overnight culture of these embryos before transfer into pseudopregnant foster mothers. The survival Rate of zygotes and their development to the two-cell and morula stage was not affected by pronuclear microinjection with different DNA-constructs or buffer. However, the development to the blastocyst stage was impaired. Nevertheless, there was no difference in blastocyst development between zygotes injected with DNA-constructs or with buffer. Neither was there a difference in cell number in in vitro cultured blastocysts resulting from pronuclear microinjection of a transgene compared with non-injected controls. The survival Rate to term was about 30% irrespective of whether microinjected embryos were transferred immediately after microinjection or after overnight culture in vitro. However, a reduction in the survival to term was observed for non-injected zygotes when they were developed in vitro to the two-cell stage before transfer to a pseudopregnant female. The percentage of Transgenic Rats that resulted from microinjected zygotes was similar in all groups regardless of the DNA-construct used (2.7-10.0%). In conclusion, the main detrimental factor in the microinjection of Rat zygotes is the introduction of solution in the pronucleus. Overnight culture of zygotes between microinjection and oviduct transfer does not decrease the efficiency of Transgenic Rat geneRation.
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Echocardiographic Evaluation of the TGR(mRen2)27 Transgenic Rat Reveals Severe Ventricular Hypertrophy and Pericardial Effusion
Pediatric Research, 1999Co-Authors: Mohammed T Numan, Barry J. Byrne, Creg H Gelband, Alok Pachori, Michael J. Katovich, Detlev Ganten, Carlos Fenario, Mohan K. RaizadaAbstract:Echocardiographic Evaluation of the TGR(mRen2)27 Transgenic Rat Reveals Severe Ventricular Hypertrophy and Pericardial Effusion
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Chronic dexamethasone treatment suppresses hypertension development in the Transgenic Rat TGR(mREN2)27.
Journal of hypertension, 1995Co-Authors: Djavidani B, Michael Bader, Maike Sander, Reinhold Kreutz, K. Zeh, Synthia H. Mellon, P. Vecsei, J. Peters, Detlev GantenAbstract:INTRODUCTION The Transgenic Rat TGR(mREN2)27 is a monogenetic Rat model in hypertension research. IntegRation of mouse Ren-2 gene into the Rat genome led to fulminant hypertension despite suppressed plasma and kidney renin concentRations. Renin is highly expressed in extrarenal tissues, especially throughout the adrenal cortex. AIMS AND METHODS Because plasma and urinary corticosteroid concentRations are elevated during the development of hypertension in these Rats, we investigated the effect of dexamethasone on blood pressure, adrenal renin and steroid metabolism. RESULTS A daily injection of 100 micrograms/kg dexamethasone for 8 weeks was capable of suppressing the development of hypertension in the Transgenic Rats. The same regimen did not alter blood pressure in Sprague-Dawley control Rats. Plasma concentRations of adrenocorticotrophic hormone (ACTH)-dependent steroids (corticosterone and 18-hydroxydeoxycorticosterone) decreased markedly in both strains treated with dexamethasone, but more pronouncedly in Transgenic Rats. Surprisingly, plasma aldosterone concentRations increased exclusively in the Transgenic Rats, and not in control Rats, treated with dexamethasone. The decrease in corticosterone and 18-hydroxydeoxycorticosterone production was accompanied by a decrease in the abundance of the messenger RNA (mRNA) encoding the Rate-limiting enzyme in steroidogenesis (P450scc cholesterol side-chain cleavage) and a decrease in the mRNA encoding P450c11 beta (11 beta-hydroxylase). The increase in aldosterone was accompanied by a massive increase in the abundance of the mRNA encoding zona glomerulosa-specific P450c11AS (aldosterone synthase), which was not increased in control Rats. CONCLUSION We conclude that ACTH-dependent steroids other than the mineralocorticoid aldosterone are responsible for the development of hypertension in the Transgenic Rat.
Stephan Von Hörsten - One of the best experts on this subject based on the ideXlab platform.
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Compensatory neuritogenesis of serotonergic afferents within the striatum of a Transgenic Rat model of Parkinson's disease.
Brain research, 2020Co-Authors: Judith Stemick, Stephan Von Hörsten, Zacharias Kohl, Carina Gauer, Jeanette Wihan, Sandra Moceri, Wei Xiang, Jürgen WinklerAbstract:Abstract The majority of patients with Parkinson’s disease (PD) suffer from L-DOPA-induced dyskinesia (LID). Besides a dysfunctional dopaminergic system, changes of the serotonergic network may be linked to this severe and adverse symptom. Particularly, serotonergic neurons have the potential to synthesize dopamine, likely associated with a disproportional dopamine release within the striatum. We hypothesized that the serotonergic system is adaptively altered in the striatum due to the reduced dopaminergic input. To answer this question, we analyzed a Transgenic Rat PD model ubiquitously expressing human α-synuclein using a bacterial artificial chromosome. Neurite analysis showed a profound loss of dopaminergic fibers by ~30–40% within the dorsal striatum paralleled by a ~50% reduction of dopaminergic neurons in the substantia nigra pars compacta. In contrast, serotonergic fibers showed an increased fiber density in the dorsal striatum by ~100%, while the number of serotonergic neurons within the raphe nuclei (RN) and its proximal neuritic processes were unaffected. Furthermore, both the dopaminergic and serotonergic fiber density remained unchanged in the neighboring motor cortex M1/M2. Interestingly, essential enzymes required for L-DOPA turnover and dopamine release were expressed in serotonergic neurons of the RN. In parallel, the serotonergic autoreceptor levels involved in a serotonergic negative feedback loop were reduced within the striatum, suggesting a dysfunctional neurotransmitter release. Overall, the increased serotonergic fiber density with its capacity for dopamine release within the striatum suggests a compensatory, site-specific serotonergic neuritogenesis. This maladaptive serotonergic plasticity may be linked to adverse symptoms such as LIDs in PD.
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Modified impact of emotion on temporal discrimination in a Transgenic Rat model of Huntington disease.
Frontiers in Behavioral Neuroscience, 2013Co-Authors: Alexis Faure, Mouna Es-seddiqi, Hoa P Nguyen, Stephan Von Hörsten, Pascale Leblanc-veyrac, Nathalie Samson-desvignes, Bruno Bozon, Bruce L. Brown, Olaf Riess, Nicole El MassiouiAbstract:Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alteRations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegeneRative process. In the Transgenic Rat model (tgHD Rats), evidence suggest emotional alteRations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstRate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous Transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstRate an alteRation of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD Rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.
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Transgenic Rat Models of Huntington's Disease.
Current topics in behavioral neurosciences, 2013Co-Authors: João Casaca Carreira, Stephan Von Hörsten, Ali Jahanshahi, Dagmar H. Zeef, Ersoy Kocabicak, Rinske Vlamings, Yasin TemelAbstract:Several animal models for Huntington’s disease (HD) have been created in order to investigate mechanisms of disease, and to evaluate the potency of novel therapies. Here, we describe the characteristics of the two Transgenic Rat models: Transgenic Rat model of HD (fragment model) and the Bacterial Artificial Chromosome HD model (full-length model). We discuss their genetic, behavioural, neuropathological and neurophysiological features.
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Early cognitive dysfunction in the HD 51 CAG Transgenic Rat model of Huntington's disease.
Behavioral neuroscience, 2012Co-Authors: Kyle D. Fink, Julien Rossignol, Andrew T. Crane, Kendra K Davis, Angela M Bavar, Nicholas Dekorver, Steven A. Lowrance, Mark P. Reilly, Michael I. Sandstrom, Stephan Von HörstenAbstract:Huntington’s disease (HD) is a neurodegeneRative disorder in humans caused by an expansion of a CAG trinucleotide repeat that produces choreic movements, which are preceded by cognitive deficits. The HD Transgenic Rat (tgHD), which contains the human HD mutation with a 51 CAG repeat allele, exhibits motor deficits that begin when these Rats are 12 months of age. However, there are no reports of cognitive dysfunction occurring prior to this. To assess whether cognitive dysfunction might precede motor deficits in tgHD Rats, one group of 9-month-old male Rats with homozygotic mutated genes and one group of wild-type (WT) Rats underwent three testing phases in a unique Spatial Operant Reversal Test (SORT) paradigm, as well as assessment of spontaneous motor activity. After testing, morphological and histological examination of the brains were made. Results indicated that tgHD Rats acquired the cued-response (Phase 1) portion of the SORT, but made significantly more errors during the reversal (Phase 2) and during the pseudorandomized reversals (Phase 3) portion of the study, when compared to WT Rats. Analysis of the data using mathematical principles of reinforcement revealed no memory, motor, or motivational deficits. These results indicate that early cognitive dysfunction, as measured by the SORT, occur prior to motor deficits, gross anatomical changes, or cell loss in the tgHD Rat with 51 CAG repeats, and suggest that this protocol could provide a useful screen for therapeutic studies.
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Memory deficits in the Transgenic Rat model of Huntington's disease.
Behavioural brain research, 2011Co-Authors: Dagmar H. Zeef, Stephan Von Hörsten, Ali Jahanshahi, Rinske Vlamings, Nick P. Van Goethem, Frédéric L.w.v.j. Schaper, Sarah Hescham, Jos Prickaerts, Yasin TemelAbstract:Abstract Memory deficits are common in patients with Huntington's disease (HD) and have a substantial impact on the quality of life of patients and their relatives. A good model resembling the human memory deficits is needed for research purposes. In this study we investigated the memory function of the Transgenic Rat model of Huntington's disease (tgHD) in the object location (OLT) and the object recognition task (ORT). Several studies have shown that the recent developed tgHD Rat model resembles the human phenotype of HD. Impairments of spatial and object recognition memory in the OLT and ORT, however, have to our knowledge not yet been reported in this Transgenic model. Our findings show that in both early and late stages of the disease the tgHD Rats have clear deficits for both visuospatial and visual object memory. Since HD patients are known to be impaired in both types of memory, these results confirm the validity of this tgHD Rat as a model for the human HD phenotype.
