Strain differences among rats in response to Remington iodine-deficient diets

International Nuclear Information System (INIS)

Okamura, K.; Taurog, A.; Krulich, L.

1981-01-01

Male rats of five different strains (Simonsen albino, Wistar, Long-Evans, Holtzman Sprague-Dawley, and Charles River Sprague-Dawley) were tested for their response to the U.S. Biochemical Corp. Remington low iodine diet containing 15-18 microgram I/kg. Measurements made after the diet had been fed for 28-30 days indicated that Simonsen albino and Wistar strains consistently showed the greatest response, based on degree of thyroid enlargement, depletion of thyroidal iodine, reduction in serum T4, and elevation of serum TSH. Long-Evans and Holtzman Sprague-Dawley rats responded relatively poorly to the low iodine diet. One experiment included female rats, and the limited data suggested that within a given strain there was no significant sex difference. With more prolonged feeding (84 days), the difference between a rapidly responding strain (Simonsen albino) and a more slowly responding strain (Holtzman Sprague-Dawley) was not so marked. Our results indicate that given sufficient time and a diet sufficiently low in iodine, even a more slowly responding strain will ultimately develop signs of extreme iodine deficiency. However, it is inconvenient and expensive to maintain rats on a Remington low iodine diet for 3 months, and studies on the effect of severe iodine deficiency are much more rapidly performed using a rapidly responding strain such as the Simonsen albino. Our observation that rats of different strains differ markedly in their responses to an iodine-deficient diet suggests that hereditary factors play an important role in this response

Differential strain vulnerability to binge eating behaviors in rats.

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Hildebrandt, Britny A; Klump, Kelly L; Racine, Sarah E; Sisk, Cheryl L

2014-03-29

Binge eating is a significantly heritable phenotype, but efforts to detect specific risk genes have fallen short. Identification of animal strain differences in risk for binge eating could highlight genetic differences across individuals of the same species that can be exploited in future animal and molecular genetic research. The current study aimed to explore strain differences in risk for binge eating in Sprague-Dawley versus Wistar female rats using the Binge Eating Resistant/Binge Eating Prone model. A sample of male Sprague-Dawley rats, a known low-risk group for binge eating, was included as a comparison group. A total of 83 rats (23 Wistar females, 30 Sprague-Dawley females, 30 Sprague-Dawley males) completed a protocol of intermittently administered, palatable food. Binge eating prone (BEP) and binge eating resistant (BER) rats were identified using a tertile approach. Sprague-Dawley female rats consumed the highest amount of palatable food and were more likely to be classified as BEP compared to Wistar female and Sprague-Dawley male rats. Wistar female rats were not significantly different from Sprague-Dawley male rats in their palatable food intake and tendency to be classified as BER rather than BEP. Sprague-Dawley female rats appear to be a particularly vulnerable genotype for binge eating. Comparisons between this group and others could help identify specific genetic/biological factors that differentiate it from lower risk groups. The reward system, linked to binge eating in humans, is a possible candidate to explore. Strain differences in the reward system could help increase understanding of individual differences in risk for binge eating in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Performance of rats orogastrically dosed with faecal strains of ...

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strains of Lactobacillus acidophilus and challenged ... Albino rats (Rattus norvegicus) were orogastrically dosed with faecal strains of Lactobacillus .... Chang et al. (2001) reported a similar observation in piglets fed probiotic strain, Lactobacillus reuteri BSA 131. Francisco et al. (1995) had earlier reported that selected ...

Enzyme markers in inbred rat strains: genetics of new markers and strain profiles.

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Adams, M; Baverstock, P R; Watts, C H; Gutman, G A

1984-08-01

Twenty-six inbred strains of the laboratory rat (Rattus norvegicus) were examined for electrophoretic variation at an estimated 97 genetic loci. In addition to previously documented markers, variation was observed for the enzymes aconitase, aldehyde dehydrogenase, and alkaline phosphatase. The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed. Linkage analysis between 35 pairwise comparisons revealed that the markers Fh-1 and Pep-3 are linked. The strain profiles of the 25 inbred strains at 11 electrophoretic markers are given.

Performance of rats orogastrically dosed with faecal strains of ...

African Journals Online (AJOL)

Albino rats (Rattus norvegicus) were orogastrically dosed with faecal strains of Lactobacillus acidophilus and simultaneously infected with Escherichia coli, while the control was challenged with E. coli alone. The treatment was repeated the second day and post ingestion period of 18 days follow. It was observed that rats ...

Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

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Takashi Kuramoto

Full Text Available Albino and hooded (or piebald rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

Small RNA expression and strain specificity in the rat

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de Bruijn Ewart

2010-04-01

Full Text Available Abstract Background Digital gene expression (DGE profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR from six different rat tissues (spleen, liver, brain, testis, heart, kidney. We describe the expression patterns of known and novel micro (miRNAs and piwi-interacting (piRNAs. Results We confirmed the expression of 588 known miRNAs (54 in antisense orientation and identified 56 miRNAs homologous to known human or mouse miRNAs, as well as 45 new rat miRNAs. Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. In accordance with earlier findings, we observed a highly tissue-specific expression pattern for all tissues analyzed. The brain was found to express the highest number of tissue-specific miRNAs, followed by testis. Notably, our experiments also revealed robust strain-specific differential miRNA expression in the liver that is caused by genetic variation between the strains. Finally, we identified two types of germline-specific piRNAs in testis, mapping either to transposons or in strand-specific clusters. Conclusions Taken together, the small RNA compendium described here advances the annotation of small RNAs in the rat genome. Strain and tissue-specific expression patterns furthermore provide a strong basis for studying the role of small RNAs in regulatory networks as well as biological process like physiology and neurobiology that are extensively studied in this model system.

The identification and characterization of novel rat hepatitis E virus strains in Bali and Sumbawa, Indonesia.

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Primadharsini, Putu Prathiwi; Mulyanto; Wibawa, I Dewa Nyoman; Anggoro, Joko; Nishizawa, Tsutomu; Takahashi, Masaharu; Jirintai, Suljid; Okamoto, Hiroaki

2018-05-01

All three genetic groups of ratHEV have been found in Indonesia, suggesting the presence of additional variants of ratHEV in unexamined areas of Indonesia. A total of 242 wild rats were captured in Bali and Sumbawa, Indonesia, during 2014-2016. Among them, 4.1% were seropositive for anti-ratHEV IgG and two (0.8%) had detectable ratHEV RNA: ratESUMBAWA-140L and ratEBali2016D-047L, sharing 84.9-85.4% and 86.9-92.1% nucleotide identity with the reported G2 strains, respectively. The provisional criteria supported the notion that the ratEBali2016D-047L and ratESUMBAWA-140L strains were novel G2 variants. These results suggested the spatial distribution of further divergent ratHEV strains in Indonesia.

Role of some selected Bifidobacterium strains in modulating immunosenescence of aged albino rats

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Hanan A. El-Bakry

2013-10-01

Full Text Available Probiotic administration has been associated with enhanced immune function in elderly subjects. However, approaches for selection of an “ideal” strain of bifidobacteria are still difficult. The aim of the present study is to investigate the possible modulatory effects of three strains of Bifidobacterium species (Bifidobacterium adolescentis ATCC 15704, Bifidobacterium breve ATCC 15700 and Bifidobacterium longum ATCC 15707 on haematological and immunological parameters of aged albino rats corresponding to normal adult ones. The animals were divided into six groups; three groups of aged rats were fed yoghurt inoculated with one of the Bifidobacterium strains; one group of aged rats was fed yoghurt alone (control aged; two groups of adult and aged rats were provided with normal diet and assigned as normal groups. The total leucocyte count was significantly increased in the three bifidobacteria-treated aged groups as compared with both normal and control aged rats. Serum IgA level was considerably increased in all treated rats. On the contrary, serum IgE level was significantly decreased in rats supplemented with yoghurt inoculated with B. adolescentis or B. breve. Both B. adolescentis and B. breve groups showed significant enhanced production of TNF-α. Furthermore, the production of cytokine IL-8 was significantly increased in the B. adolescentis group. Interestingly, it was apparent that only B. adolescentis had the most pronounced effect on aged rats to regain nearly normal values as measured in normal adult rats. Conclusively, the present work indicates that dietary consumption of selected bifidobacteria strains may have a particular application in the elderly especially in terms of immunomodulation.

Renal blood flow dynamics in inbred rat strains provides insight into autoregulation.

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A Mitrou, Nicholas G; Cupples, William A

2014-01-01

Renal autoregulation maintains stable renal blood flow in the face of constantly fluctuating blood pressure. Autoregulation is also the only mechanism that protects the delicate glomerular capillaries when blood pressure increases. In order to understand autoregulation, the renal blood flow response to changing blood pressure is studied. The steadystate response of blood flow is informative, but limits investigation of the individual mechanisms of autoregulation. The dynamics of autoregulation can be probed with transfer function analysis. The frequency-domain analysis of autoregulation allows investigators to probe the relative activity of each mechanism of autoregulation. We discuss the methodology and interpretation of transfer function analysis. Autoregulation is routinely studied in the rat, of which there are many inbred strains. There are multiple strains of rat that are either selected or inbred as models of human pathology. We discuss relevant characteristics of Brown Norway, Spontaneously hypertensive, Dahl, and Fawn-Hooded hypertensive rats and explore differences among these strains in blood pressure, dynamic autoregulation, and susceptibility to hypertensive renal injury. Finally we show that the use of transfer function analysis in these rat strains has contributed to our understanding of the physiology and pathophysiology of autoregulation and hypertensive renal disease.Interestingly all these strains demonstrate effective tubuloglomerular feedback suggesting that this mechanism is not sufficient for effective autoregulation. In contrast, obligatory or conditional failure of the myogenic mechanism suggests that this component is both necessary and sufficient for autoregulation.

Immune Modulating Capability of Two Exopolysaccharide-Producing Bifidobacterium Strains in a Wistar Rat Model

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Nuria Salazar

2014-01-01

Full Text Available Fermented dairy products are the usual carriers for the delivery of probiotics to humans, Bifidobacterium and Lactobacillus being the most frequently used bacteria. In this work, the strains Bifidobacterium animalis subsp. lactis IPLA R1 and Bifidobacterium longum IPLA E44 were tested for their capability to modulate immune response and the insulin-dependent glucose homeostasis using male Wistar rats fed with a standard diet. Three intervention groups were fed daily for 24 days with 10% skimmed milk, or with 109 cfu of the corresponding strain suspended in the same vehicle. A significant increase of the suppressor-regulatory TGF-β cytokine occurred with both strains in comparison with a control (no intervention group of rats; the highest levels were reached in rats fed IPLA R1. This strain presented an immune protective profile, as it was able to reduce the production of the proinflammatory IL-6. Moreover, phosphorylated Akt kinase decreased in gastroctemius muscle of rats fed the strain IPLA R1, without affecting the glucose, insulin, and HOMA index in blood, or levels of Glut-4 located in the membrane of muscle and adipose tissue cells. Therefore, the strain B. animalis subsp. lactis IPLA R1 is a probiotic candidate to be tested in mild grade inflammation animal models.

The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

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Oliff, H S; Marek, P; Miyazaki, B; Weber, E

1996-08-26

The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

NARCIS (Netherlands)

Bohus, B.; Wimersma Greidanus, T.B. van; Wied, D. de

Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits

Evaluation of the use of various rat strains for immunogenic potency tests of Sabin-derived inactivated polio vaccines.

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Someya, Yuichi; Ami, Yasushi; Takai-Todaka, Reiko; Fujimoto, Akira; Haga, Kei; Murakami, Kosuke; Fujii, Yoshiki; Shirato, Haruko; Oka, Tomoichiro; Shimoike, Takashi; Katayama, Kazuhiko; Wakita, Takaji

2018-03-01

Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

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Hughes, Robert N; Hancock, Nicola J

2016-01-01

To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males. Copyright © 2015 Elsevier Inc. All rights reserved.

Strain differences of cadmium-induced hepatotoxicity in Wistar-Imamichi and Fischer 344 rats: involvement of cadmium accumulation

International Nuclear Information System (INIS)

Shimada, Hideaki; Takamure, Yasutaka; Shimada, Akinori; Yasutake, Akira; Waalkes, Michael P.; Imamura, Yorishige

2004-01-01

We previously reported that Wistar-Imamichi (WI) rats have a strong resistance to cadmium (Cd)-induced lethality compared to other strains such as Fischer 344 (Fischer) rats. The present study was designed to establish biochemical and histological differences in Cd toxicity in WI and Fischer rats, and to clarify the mechanistic basis of these strain differences. A single Cd (4.5 mg/kg, s.c.) treatment caused a significant increase in serum alanine aminotransferase activity, indicative of hepatotoxicity, in Fischer rats, but did not in WI rats. This difference in hepatotoxic response to Cd was supported by pathological analysis. After treatment with Cd at doses of 3.0, 3.5 and 4.5 mg/kg, the hepatic and renal accumulation of Cd was significantly lower in the WI rats than in the Fischer rats, indicating a kinetic mechanism for the observed strain differences in Cd toxicity. Thus, the remarkable resistance to Cd-induced hepatotoxicity in WI rats is associated, at least in part, with a lower tissue accumulation of the metal. Hepatic and renal zinc (Zn) contents after administration were similarly lower in WI than in Fischer rats. When Zn was administered in combination with Cd to Fischer rats, it decreased Cd contents in the liver and kidney, and exhibited a significant protective effect against the toxicity of Cd. We propose the possibility that Zn transporter plays an important role in the strain difference of Cd toxicity in WI and Fischer rats

Expression profiling of the VKORC1 and Calumenin gene in a Danish strain of bromadiolone-resistant Norway rats

DEFF Research Database (Denmark)

Markussen, Mette Drude; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

in European strains of Norway rats while high hepatic levels of calumenin has been suggested responsible for resistance in an US strain of rats. To characterize the resistance mechanism in a Danish strain of bromadiolone-resistant Norway rats (with an Y139C-VKORC1 mutation), we compared VKORC1 and Calumenin......Anticoagulant resistance in Norway rats (Rattus norvegicus) has been associated with two genes, VKORC1 and Calumenin, which encodes proteins essential to the vitamin K-dependent gamma-carboxylation system. Mutations in the VKORC1 gene are considered the genetic basis for anticoagulant resistance...... liver gene expression between resistant and anticoagulant-susceptible rats upon saline and bromadiolone-administration. The resistant male and female rats had significantly lower constitutive VKORC1 expression (57 % and 63 %) compared to the susceptible rats (100 %) while the constitutive Calumenin...

Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

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Maryam Salehi

2016-02-01

Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

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2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

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Harishankar, N; Vajreswari, A; Giridharan, N V

2011-09-01

WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to

Rat strains differ in susceptibility to Ureaplasma parvum-induced urinary tract infection and struvite stone formation.

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Reyes, Leticia; Reinhard, Mary; O'donell, L J; Stevens, Janet; Brown, Mary B

2006-12-01

Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1alpha (IL-1alpha), and IL-1beta. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues.

Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

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Denise eManahan-Vaughan

2011-03-01

Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

Strain difference of cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats

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Shimada, Hideaki; Narumi, Rika [Kumamoto University, Faculty of Education, Kumamoto (Japan); Nagano, Masaaki; Yasutake, Akira [National Institute for Minamata Disease, Biochemistry Section, Kumamoto (Japan); Waalkes, Michael P. [National Cancer Institute at the National Institute of Environmental Health Sciences, Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Research Triangle Park, NC (United States); Imamura, Yorishige [Kumamoto University, Graduate School of Pharmaceutical Sciences, Kumamoto (Japan)

2009-07-15

Previously, we reported that Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl{sub 2}, sc and killed 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathological and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), the testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, the testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that the testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats. (orig.)

Morphological and functional changes in the rat heart after X irradiation: Strain differences

International Nuclear Information System (INIS)

Yeung, T.K.; Lauk, S.; Simmonds, R.H.; Hopewell, J.W.; Trott, K.R.

1989-01-01

The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change

Rat Strains Differ in Susceptibility to Ureaplasma parvum-Induced Urinary Tract Infection and Struvite Stone Formation▿

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Reyes, Leticia; Reinhard, Mary; O'Donell, L. J.; Stevens, Janet; Brown, Mary B.

2006-01-01

Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1α (IL-1α), and IL-1β. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues. PMID:16982825

Strain differences in the response to morphine on incorporation of 3H-lysine into rat brain protein

International Nuclear Information System (INIS)

Ford, D.H.; Rhines, R.K.; Levi, M.A.

1977-01-01

The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FFA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains. SA of the lysine in cerebral cortical protein increased in both strains with time. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. It is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats. (author)

Effect of stress on variability of systemic hemodynamics in rats of various genetic strains.

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Belkina, L M; Tarasova, O S; Kirillina, T N; Borovik, A S; Popkova, E V

2003-09-01

Power spectral density of heart rate fluctuations in the range of 0.02-5.00 Hz in August rats was lower than in Wistar rats. Changes in mean blood pressure and heart rate during stress (15-min immobilization) were similar in animals of both strains. As differentiated from Wistar rats, power spectral density of fluctuations in August rats considerably decreased after stress. August rats were characterized by low spectral power at rest and high resistance to the arrhythmogenic effect of 10-min acute myocardial ischemia.

Measurement of the uniaxial mechanical properties of rat skin using different stress-strain definitions.

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Karimi, A; Navidbakhsh, M

2015-05-01

The mechanical properties of skin tissue may vary according to the anatomical locations of a body. There are different stress-strain definitions to measure the mechanical properties of skin tissue. However, there is no agreement as to which stress-strain definition should be implemented to measure the mechanical properties of skin at different anatomical locations. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are employed to determine the mechanical properties of skin tissue at back and abdomen locations of a rat body. The back and abdomen skins of eight rats are excised and subjected to a series of tensile tests. The elastic modulus, maximum stress, and strain of skin tissues are measured using three stress definitions and four strain definitions. The results show that the effect of varying the stress definition on the maximum stress measurements of the back skin is significant but not when calculating the elastic modulus and maximum strain. No significant effects are observed on the elastic modulus, maximum stress, and strain measurements of abdomen skin by varying the stress definition. In the true stress-strain diagram, the maximum stress (20%), and elastic modulus (35%) of back skin are significantly higher than that of abdomen skin. The true stress-strain definition is favored to measure the mechanical properties of skin tissue since it gives more accurate measurements of the skin's response using the instantaneous values. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

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Andersson, I M; Lorentzen, J C; Ericsson-Dahlstrand, A

2000-11-01

Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal

A high frequency of induction of chromosome aberrations in the bone marrow cells of LEC strain rats by X-irradiation

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Okui, Toyo (Hokkaido Inst. of Public Health, Sapporo (Japan)); Hayashi, Masanobu; Watanabe, Tomomasa; Namioka, Shigeo (Dept. of Lab. Animal Science, Hokkaido Univ., Sapporo (Japan)); Endoh, Daiji; Sato, Fumiaki (Dept. of Radiation Biology, Faculty of Veterinary Medicine, Hokkaido Univ., Sapporo (Japan)); Kasai, Noriyuki (Inst. for Animal Experimentation, Hokkaido Univ., Sapporo (Japan))

1994-08-01

LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, are highly sensitive to whole-body X-irradiation when compared to WKAH strain rats. The present results showed that the frequencies of all types of chromosome aberrations induced by X-irradiation in the bone marrow cells of LEC rats were approximately 2- to 3-fold higher than those of WKAH rats, though no significant difference was observed in the frequency of spontaneous chromosome aberrations between LEC and WKAH rats.

Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

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Del-Bel E.A.

1997-01-01

Full Text Available The effect of acute (120 mg/kg and chronic (25 mg/kg, twice a day, for 4 days intraperitonial injection of the nitric oxide (NO synthase (NOS inhibitor NG-nitro-L-arginine (L-NOARG was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ and by sound stimulation of audiogenic seizure-resistant (R and audiogenic seizure-susceptible (S rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg and protected against PTZ-induced tonic seizures (80 mg/kg. The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.

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Kearns, David N; Gomez-Serrano, Maria A; Weiss, Stanley J; Riley, Anthony L

2006-05-15

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

Erythrocyte phosphofructokinase in rat strains with genetically determined differences in 2,3-diphosphoglycerate levels.

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Noble, N A; Tanaka, K R

1981-02-01

We have studied the erythrocyte enzyme phosphofructokinase (PFK) from two strains of Long-Evans rats with genetically determined differences in erythrocyte 2,3-diphosphoglycerate (DPG) levels. The DPG difference is due to two alleles at one locus. With one probable exception, the genotype at this locus is always associated with the hemoglobin (Hb) electrophoretic phenotype, due to a polymorphism at the III beta-globin locus. The enzyme PFK has been implicated in the DPG difference because glycolytic intermediate levels suggest that this enzyme has a higher in vivo activity in High-DPG strain rats, although the total PFK activity does not differ. We report here that partially purified erythrocyte PFK from Low-DPG strain cells is inhibited significantly more at physiological levels of DPG (P less than 0.01) than PFK from High-DPG strain erythrocytes. Citrate and adenosine triphosphate also inhibit the Low-DPG enzyme more than the High-DPG enzyme. Therefore, a structurally different PFK, with a greater sensitivity to inhibitors, may explain the lower DPG and ATP levels observed in Low-DPG strain animals. These data support a two-locus (Hb and PFK) hypothesis and provide a gene marker to study the underlying genetic and physiologic relationships of these loci.

Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

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Belda, Xavier; Márquez, Cristina; Armario, Antonio

2004-10-05

We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strains.

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Carrasco, Javier; Márquez, Cristina; Nadal, Roser; Tobeña, Adolfo; Fernández-Teruel, Albert; Armario, Antonio

2008-05-01

Several studies performed in outbred Roman high- and low-avoidance lines (RHA and RLA, respectively) have demonstrated that the more anxious line (RLA) is characterized by a higher hypothalamic-pituitary-adrenal (HPA) response to certain stressors than the less anxious one (RHA). However, inconsistent results have also been reported. Taking advantage of the generation of an inbred colony of RLA and RHA rats (RHA-I and RLA-I, respectively), we have characterized in the two strains not only resting and stress levels of peripheral HPA hormones but also central components of the HPA axis, including CRF gene expression in extra-hypothalamic areas. Whereas resting levels of ACTH and corticosterone did not differ between the strains, a greater response to a novel environment was found in RLA-I as compared to RHA-I rats. RLA-I rats showed enhanced CRF gene expression in the paraventricular nucleus (PVN) of the hypothalamus, with normal arginin-vasopressin gene expression in both parvocellular and magnocellular regions of the PVN. This enhanced CRF gene expression is not apparently related to altered negative corticosteroid feedback as similar levels of expression of brain glucorticoid and mineralocorticoid receptors were found in the two rat strains. CRF gene expression tended to be higher in the central amygdala and it was significantly higher in the dorsal region of the bed nucleus of stria terminalis (BNST) of RLA-I rats, while no differences appeared in the ventral region of BNST. Considering the involvement of CRF and the BNST in anxiety and stress-related behavioral alterations, the present data suggest that the CRF system may be a critical neurobiological substrate underlying differences between the two rat strains.

Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

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We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

Electrophoretic variation in low molecular weight lens crystallins from inbred strains of rats.

Science.gov (United States)

Donner, M E; Skow, L C; Kunz, H W; Gill, T J

1985-10-01

Analysis of rat lens soluble proteins by analytical isoelectric focusing detected two inherited electrophoretic differences in low molecular weight (LM) crystallins from inbred strains of rats (Rattus norvegicus). The polymorphic lens crystallins were shown to be similar to a genetically variant LM crystallin, LEN-1, previously described in mice (Mus musculus) and encoded on chromosome 1, at a locus linked to Pep-3 (dipeptidase). Linkage analysis demonstrated that the rat crystallin locus was loosely linked to Pep-3 at a recombination distance of 38 +/- 4.5 U. These data suggest the conservation of a large chromosomal region during the evolution of Rodentia and support the hypothesis that the gamma-crystallins are evolving more rapidly than alpha- or beta-crystallins.

A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

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McIntosh, G H; Royle, P J; Playne, M J

1999-01-01

Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

Pediocin PA-1 and a pediocin producing Lactobacillus plantarum strain do not change the HMA rat microbiota

DEFF Research Database (Denmark)

Bernbom, Nete; Jelle, N.B.; Brogren, C.-H.

2009-01-01

microbiota was in all treatments dominated by lactic acid bacteria and coliforms and no changes in the rat commensal microbiota were detected after ingestion of either of the two L plantarum strains as determined by both culturable methods and molecular methods (DGGE). Both strains were detected...

Prebiotic and synbiotic effects on rats fed malted barley with selected bacteria strains

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Yadong Zhong

2014-10-01

Full Text Available Background: Butyric acid, one of the key products formed when β-glucans are degraded by the microbiota in the colon, has been proposed to be important for colonic health. Glutamine bound to the fibre may have similar effects once it has been liberated from the fibre in the colon. Both β-glucans and glutamine are found in high amounts in malted barley. Lactobacillus rhamnosus together with malt has been shown to increase the formation of butyric acid further in rats. Objective: To investigate whether Lactobacillus rhamnosus 271, Lactobacillus paracasei 87002, Lactobacillus plantarum HEAL 9 and 19, and Bifidobacterium infantis CURE 21 affect the levels of short-chain fatty acids and glutamine in caecum and portal blood of rats fed barley malt. Design: The experimental diets were fed for 12 days. The daily dose of the probiotic strain was 1×109 colony forming units and the intake of fibre 0.82 g/day. Results: The malt mostly contained insoluble fibre polymers (93%, consisting of glucose and xylose (38–41 g/kg and some arabinose (21 g/kg. The fibre polysaccharides were quite resistant to fermentation in the rats, regardless of whether or not probiotics were added (25–30% were fermented. Caecal and portal levels of acetic acid decreased in the rats after the addition of L. plantarum HEAL 9 and L. rhamnosus 271, and also the levels of butyric acid. Viable counts of Lactobacillus, Bifidobacterium and Enterobacteriaceae were unaffected, while the caecal composition of Lactobacilli was influenced by the type of strain administrated. Portal levels of glutamine were unchanged, but glycine levels increased with L. plantarum HEAL 9 and 19 and phenylalanine with L. rhamnosus 271. Conclusions: Although the probiotic strains survived and reached the caecum, except B. infantis CURE 21, there were no effects on viable counts or in the fermentation of different fibre components, but the formation of some bacterial metabolites decreased. This may be due to

IMPACT OF GENETIC STRAIN ON BODY FAT LOSS, FOOD CONSUMPTION, METABOLISM, VENTILATION, AND MOTOR ACTIVITY IN FREE RUNNING FEMALE RATS

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U.S. Environmental Protection Agency — Physiologic data associated with different strains of common laboratory rat strains. This dataset is associated with the following publication: Gordon , C., P....

Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats

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Lauren Izabel Medeiros Couto

2015-08-01

Full Text Available ABSTRACTOBJECTIVE: To evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats. METHODS: Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG, after induction of injuries, the rats were observed for 24 h. In the simulation group (SG and the arginine group (AG respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK, lactic dehydrogenase (LDH, aspartate aminotransferase (AST and C-reactive protein (CRP. The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's tmethods were used and p≤ 0.05 was taken to be statistically significant. RESULTS: In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis. CONCLUSION: Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain.

Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

International Nuclear Information System (INIS)

Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

1996-01-01

The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

Strain-specific response to anaesthetics and analgesics in rat and rabbit : A pharmacogenetic approach

NARCIS (Netherlands)

Avsaroglu, H.

2008-01-01

The response of (laboratory) animals to anaesthetics and analgesics is known to show intraspecies variability. Apart from environmental influences, this may also be caused by genetic factors. In this thesis, rabbit and rat inbred strains were used to identify differences in response to anaesthetics

Use of micro-CT-based finite element analysis to accurately quantify peri-implant bone strains: a validation in rat tibiae.

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Torcasio, Antonia; Zhang, Xiaolei; Van Oosterwyck, Hans; Duyck, Joke; van Lenthe, G Harry

2012-05-01

Although research has been addressed at investigating the effect of specific loading regimes on bone response around the implant, a precise quantitative understanding of the local mechanical response close to the implant site is still lacking. This study was aimed at validating micro-CT-based finite element (μFE) models to assess tissue strains after implant placement in a rat tibia. Small implants were inserted at the medio-proximal site of 8 rat tibiae. The limbs were subjected to axial compression loading; strain close to the implant was measured by means of strain gauges. Specimen-specific μFE models were created and analyzed. For each specimen, 4 different models were created corresponding to different representations of the bone-implant interface: bone and implant were assumed fully osseointegrated (A); a low stiffness interface zone was assumed with thickness of 40 μm (B), 80 μm (C), and 160 μm (D). In all cases, measured and computational strains correlated highly (R (2) = 0.95, 0.92, 0.93, and 0.95 in A, B, C, and D, respectively). The averaged calculated strains were 1.69, 1.34, and 1.15 times higher than the measured strains for A, B, and C, respectively, and lower than the experimental strains for D (factor = 0.91). In conclusion, we demonstrated that specimen-specific FE analyses provide accurate estimates of peri-implant bone strains in the rat tibia loading model. Further investigations of the bone-implant interface are needed to quantify implant osseointegration.

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling.

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Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I

2015-08-03

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na(+)/Ca(2+) exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

Science.gov (United States)

Andrews, J S; Jansen, J H; Linders, S; Princen, A; Broekkamp, C L

1995-04-01

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequence analysis of Drd2, Drd4, and Dat1 in SHR and WKY rat strains

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Mill Jonathan

2005-12-01

Full Text Available Abstract Background The Spontaneously Hypertensive Rat (SHR shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression. Methods We sequenced three candidate dopaminergic genes (Drd2, Drd4, and Dat1 in the SHR and WKY to identify between-strain sequence differences. Results No between-strain sequence differences were found in either Drd2 or Drd4, but several variations were found in the Dat1 gene that encodes the dopamine transporter. Conclusion It is plausible that DNA sequence changes in the Dat1 gene account for some of the behavioural differences observed between the SHR and WKY strains. Future work will focus on elucidating the functional effects of the observed polymorphisms.

Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

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Takahashi R.N.

2001-01-01

Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat.

Data.gov (United States)

U.S. Environmental Protection Agency — Body composition data for common laboratory strains of rat as a function of age. This dataset is associated with the following publication: Gordon , C., K. Jarema ,...

A Novel Reporter Rat Strain That Conditionally Expresses the Bright Red Fluorescent Protein tdTomato.

Directory of Open Access Journals (Sweden)

Hiroyuki Igarashi

Full Text Available Despite the strength of the Cre/loxP recombination system in animal models, its application in rats trails that in mice because of the lack of relevant reporter strains. Here, we generated a floxed STOP tdTomato rat that conditionally expresses a red fluorescent protein variant (tdTomato in the presence of exogenous Cre recombinase. The tdTomato signal vividly visualizes neurons including their projection fibers and spines without any histological enhancement. In addition, a transgenic rat line (FLAME that ubiquitously expresses tdTomato was successfully established by injecting intracytoplasmic Cre mRNA into fertilized ova. Our rat reporter system will facilitate connectome studies as well as the visualization of the fine structures of genetically identified cells for long periods both in vivo and ex vivo. Furthermore, FLAME is an ideal model for organ transplantation research owing to improved traceability of cells/tissues.

Comparative Study of Histopathologic Characterization of Azoxymethane-induced Colon Tumors in Three Inbred Rat Strains

DEFF Research Database (Denmark)

Kobæk Larsen, Morten; Fenger, Claus; Hansen, Ket

2002-01-01

To obtain controlled genetic variation, colon cancer was chemically induced by use of four subcutaneous injections of azoxymethane (15 mg/kg of body weight/wk) to rats of 3 inbred strains (BDIX/OrlIco, F344/NHsd, WAG/Rij). The selection was based on the availability of established colon cancer cell...

Effects of Long Duration Noise Exposure on Hearing and Health

Science.gov (United States)

1975-11-01

defects of the eye, tail, hind- and forefoot. Geber and Anderson studied the effect:.-, of chronic intermittent noise stress on the body weight...Stimulus. Amer.Jour. Physiol.212, 1967, pp.1174-1178. Geber , W.F.: Developmental f.ffects of Chronic Maternal Audiovisual Stress on the Rat Fetus...Jour. Emb.Exp.Morph., 16, 1966, pp.1-16. Geber , W.F. and Anderson, T.A.: Cardiac Hypertrophy Due to Chronic Audiogenic Stress in the Rat and

The WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression [corrected].

Science.gov (United States)

Sarkisova, Karine; van Luijtelaar, Gilles

2011-06-01

A great number of clinical observations show a relationship between epilepsy and depression. Idiopathic generalized epilepsy, including absence epilepsy, has a genetic basis. The review provides evidence that WAG/Rij rats can be regarded as a valid genetic animal model of absence epilepsy with comorbidity of depression. WAG/Rij rats, originally developed as an animal model of human absence epilepsy, share many EEG and behavioral characteristics resembling absence epilepsy in humans, including the similarity of action of various antiepileptic drugs. Behavioral studies indicate that WAG/Rij rats exhibit depression-like symptoms: decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased sucrose consumption and preference (anhedonia). In addition, WAG/Rij rats adopt passive strategies in stressful situations, express some cognitive disturbances (reduced long-term memory), helplessness, and submissiveness, inability to make choice and overcome obstacles, which are typical for depressed patients. Elevated anxiety is not a characteristic (specific) feature of WAG/Rij rats; it is a characteristic for only a sub-strain of WAG/Rij rats susceptible to audiogenic seizures. Interestingly, WAG/Rij rats display a hyper-response to amphetamine similar to anhedonic depressed patients. WAG/Rij rats are sensitive only to chronic, but not acute, antidepressant treatments, suggesting that WAG/Rij rats fulfill a criterion of predictive validity for a putative animal model of depression. However, more and different antidepressant drugs still await evaluation. Depression-like behavioral symptoms in WAG/Rij rats are evident at baseline conditions, not exclusively after stress. Experiments with foot-shock stress do not point towards higher stress sensitivity at both behavioral and hormonal levels. However, freezing behavior (coping deficits) and blunted response of 5HT in the frontal cortex to uncontrollable sound stress

Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

Science.gov (United States)

Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

2006-06-15

Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

Abnormal G1 arrest in the cell lines from LEC strain rats after X-irradiation

International Nuclear Information System (INIS)

Hayashi, M.; Uehara, K.; Kirisawa, R.; Endoh, D.; Arai, S.; Okui, T.

1997-01-01

The effect of X-irradiation of cell lines from LEC and WKAH strain rats on a progression o cell cycle was investigated. When WKAH rat ells were exposed to 5 Gy of X-rays and their cell cycle distribution was determined by a flow cytometer, the proportion of S-phase cells decrease and that of G2/M-phase cells in creased at 8 hr post-irradiation. At 18 and 24 hr post-irradiation, approximately 80% of the cells appeared in the G1 phase. On the contrary, the proportion of S-phase cells increased and that of G1-phase cells decreased in LEC rats during 8-24 hr post-irradiation, compared with that at 0 hr post-irradiation. Thus, radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed inWKAH rat cells but not in LEC rat cells. In the case of WKAH rat cells, the intensities of the bands of p53 protein increased at 1 and 2 hr after X-irradiation at 5 Gy, compared with those of un-irradiated cells and at 0 hr post-irradiation. In contrast, the intensities of the bands were faint and did not significantly increase in LEC rat ells during 0-6 hr incubation after X-irradiation. Present results suggested that the radioresistant DNA synthesis in LEC rat cells is thought to be due to the abnormal G1 arrest following X-irradiation

Avoidance Expression in Rats as a Function of Signal-Shock Interval: Strain and Sex Differences

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Richard J Servatius

2015-07-01

Full Text Available Inbred Wistar Kyoto (WKY rats express inhibited temperament, increased sensitivity to stress, and exaggerated expressions of avoidance. A long-standing observation for lever press escape/avoidance learning in rats is the duration of the warning signal (WS determines whether avoidance is expressed over escape. Outbred female Sprague-Dawley (SD rats trained with a 10-s WS efficiently escaped, but failed to exhibit avoidance; avoidance was exhibited to a high degree with WSs longer than 20-s. We examined this longstanding WS duration function and extended it to male SD and male and female WKY rats. A cross-over design with two WS durations (10 s or 60 s was employed. Rats were trained (20 trials/session in four phases: acquisition (10 sessions, extinction (10 sessions, re-acquisition (8 sessions and re-extinction (8 sessions. Consistent with the literature, female and male SD rats failed to express avoidance to an appreciable degree with a 10-s WS. When these rats were switched to a 60-s WS, performance levels in the initial session of training resembled the peak performance of rats trained with a 60-s WS. Therefore, the avoidance relationship was acquired, but not expressed at 10-s WS. Further, poor avoidance at 10-s does not adversely affect expression at 60-s. Failure to express avoidance with a 10-s WS likely reflects contrasting reinforcement value of avoidance, not a reduction in the amount of time available to respond or competing responses. In contrast, WKY rats exhibited robust avoidance with a 10-s WS, which was most apparent in female WKY rats. Exaggerated expression of avoidances by WKY rats, especially female rats, further confirms this inbred strain as a model of anxiety vulnerability.

Caloric restriction in lean and obese strains of laboratory rat: effects on body composition, metabolism, growth and overall health

Data.gov (United States)

U.S. Environmental Protection Agency — Data related to obese and lean strains of rat commonly used in the laboratory that are calorically restricted and its effects on physiologic parameters (Body...

An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

Science.gov (United States)

Karimi, Alireza; Navidbakhsh, Mahdi

2014-07-01

There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

CRISPR/Cas9-mediated targeting of the Rosa26 locus produces Cre reporter rat strains for monitoring Cre-loxP-mediated lineage tracing.

Science.gov (United States)

Ma, Yuanwu; Yu, Lei; Pan, Shuo; Gao, Shan; Chen, Wei; Zhang, Xu; Dong, Wei; Li, Jing; Zhou, Rui; Huang, Lan; Han, Yunlin; Bai, Lin; Zhang, Li; Zhang, Lianfeng

2017-10-01

The rat is an important laboratory animal for physiological, toxicological and pharmacological studies. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) is a simple and efficient tool to generate precise genetic modifications in rats, which will promote the accumulation of genetic resources and enable more precise studies of gene function. To monitor Cre-loxP-mediated excision in vivo, we generated a Cre reporter rat strain (Rosa26-imCherry) by knockin of a Cre reporter cassette at the Rosa26 locus using CRISPR/Cas9. Rosa26-imCherry rats exhibited inducible expression of the mCherry cassette (imCherry) using the Cre-loxP system, whereas normal rats exhibited ubiquitous expression of eGFP but not mCherry in the whole body. Injection of adeno-associated virus serotype 9-Cre into the hippocampus and skeletal muscle resulted in mCherry expression in virus-infected cells. Cre-loxP-mediated mCherry expression was then evaluated by crossing Rosa26-imCherry rats with transgenic rats ubiquitously expressing CAG-Cre, heart-specific α-MHC-Cre transgenic rats and liver-specific Alb-Cre knockin rats. Finally, using the established system the expression pattern of Cre driven by two endogenous gene promoters (Wfs1-Cre knockin rat, FabP2-Cre knockin rat) was traced. In summary, we demonstrated excision of the loxP-flanked allele in Rosa26-imCherry rats via activation of mCherry expression in the presence of Cre recombinase. This newly established Rosa26-imCherry rat strain represents a useful tool to facilitate Cre-expression pattern determination and tracing experiments. © 2017 Federation of European Biochemical Societies.

Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).

Science.gov (United States)

Swedberg, M D; Jacobsen, P; Honoré, T

1995-09-01

The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.

Immunohistochemical characterisation of the local immune response in azoxymethane-induced colon tumours in the BDIX inbred rat strain

DEFF Research Database (Denmark)

Kobæk Larsen, Morten; Diederichsen, Axel Cosmus Pyndt; Agger, Ralf

2004-01-01

by four weekly subcutaneous azoxymethane injections in inbred rats of the BDIX/OrlIco strain in two separate studies. Azoxymethane-induced tumours show many similarities to spontaneously occurring human colon carcinomas with respect to histopathological appearance. In our studies, the overall inflammatory...

Comparative physicochemical and biological properties of two strains of Kilham rat virus, a non-defective parvovirus

Energy Technology Data Exchange (ETDEWEB)

Mitra, S.; Snyder, C.E.; Bates, R.C.; Banerjee, P.T.

1982-01-01

Two antigenically indistinguishable strains, 171 and 308, of Kilham rat virus (KRV) have distinct host ranges and contain capsid proteins of identical size, but with different isoelectric points. The single-stranded DNA genomes of the viruses are also the same size but appear to have different secondary and tertiary structures. The genomes of the two strains have nearly identical cleavage maps for 11 restriction endonucleases. However, there is a lack of extended heteroloy in the nucleotide sequence of the two virus genomes, as judged by electron microscopic analysis of the heteroduplex of the two virus DNAs. This suggests that very subtle differences in the sequences of the genome, and possibly of the capsid proteins, may play a role in the host specificity without affecting the antigenic similarity of KRV strains.

Influence of age, strain and season on circadian periodicity of pituitary, gonadal and adrenal hormones in the serum of male laboratory rats.

Science.gov (United States)

Wong, C C; Döhler, K D; Geerlings, H; von zur Mühlen, A

1983-01-01

The influence of age, strain and season on the circadian pattern of serum levels of LH, FSH, prolactin androgens and corticosterone was studied in five groups of male laboratory rats. Significant 24-hour periodicity was observed for serum levels of corticosterone in all five groups, for androgen levels in four, for prolactin levels in three, for LH levels in two and for FSH levels in one group of rats. There were significant influences of age, strain and season on the temporal patterns and/or on 24-hour mean serum hormone levels. The results indicate that some of the disagreements on existence or nonexistence of circadian rhythms and on rhythm patterns in serum hormone levels may be explained by the fact that animals of different ages or strains had been used or that experiments were performed at different times of the year.

Strain-dependent differences in sensitivity of rat beta-cells to interleukin 1 beta in vitro and in vivo

DEFF Research Database (Denmark)

Reimers, J I; Andersen, H U; Mauricio, D

1996-01-01

/kg) or vehicle for 5 days. All the strains investigated were susceptible to IL-1 beta-induced changes in body weight, food intake, temperature, and plasma glucagon and corticosterone. However, IL-1 beta induced hyperglycemia and impairment of beta-cell glucose responsiveness in WK/Mol and LS/Mol rats...

Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

Science.gov (United States)

Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

2015-01-01

Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats

Science.gov (United States)

TANAKA, Masami; WATANABE, Minoru; YOKOMI, Izuru; MATSUMOTO, Naoki; SUDO, Katsuko; SATOH, Hitoshi; IGARASHI, Tsuneo; SEKI, Azusa; AMANO, Hitoshi; OHURA, Kiyoshi; RYU, Kakei; SHIBATA, Shunichi; NAGAYAMA, Motohiko; TANUMA, Jun-ichi

2014-01-01

Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats. PMID:25736479

Characterization of Bromadiolone Resistance in a Danish Strain of Norway Rats, Rattus norvegicus, by Hepatic Gene Expression Profiling of VKORC1 and Calumenin

DEFF Research Database (Denmark)

Markussen, Mette Drude; Heiberg, Ann-Charlotte; Fredholm, Merete

2007-01-01

Anticoagulant agents, such as warfarin and bromadiolone, are used to control populations of Norway rats (Rattus norvegicus). The anticoagulants compromise the blood-coagulation process by inhibiting the vitamin K2,3 epoxide reductase enzyme complex (VKOR). Mutations in the VKORC1 gene, encoding...... (with an Y139C-VKORC1 mutation), we compared VKORC1 and calumenin liver gene expression between resistant and anticoagulant-susceptible rats upon saline and bromadiolone-administration. Additionally, we established the effect of bromadiolone on VKORC1 and calumenin expression in the two rat strains....... Bromadiolone had no effect on gene expression in resistant rats but significantly induced calumenin expression in susceptible rats. Calumenin expression was similar between resistant and susceptible rats upon saline administration but two-fold lower in resistant rats upon bromadiolone-treatment. These results...

Fischer 344 and Lewis rat strains as a model of genetic vulnerability to drug addiction

Directory of Open Access Journals (Sweden)

Cristina eCadoni

2016-02-01

Full Text Available Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60 % of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis to differences in mesolimbic dopamine (DA transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neurons functionality.Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigations, results from the reviewed studies might open new vistas in

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.

Science.gov (United States)

Cadoni, Cristina

2016-01-01

Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant

Caloric Restriction in Lean and Obese Strains of Laboratory ...

Science.gov (United States)

NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improved longevity with caloric restriction (CR) in rodents. Little is known regarding effects of CR in genetically lean versus obese strains. Long-Evans (LE) and Brown Norway (BN) rats make an ideal comparison for a CR study because the percentage body fat of young adult LE rats is double that of BN rats. Male LE and BN rats were either fed ad libitum (AL) or were caloricallyrestricted to 80 or 90% of their AL weight. The percentages of fat, lean and fluid mass were measured non-invasively at 2- to 4-week intervals. Metabolic rate and respiratory quotient were measured after 3, 6, 9 and 12 months of CR. Overall health was scored monthly. The percentage of fat of the LE strain decreased with CR, whereas the percentage of fat of the BN strain remained above the AL group for several months. The percentage of lean mass increased above the AL for both strains subjected to CR. The percentage offluid was unaffected by CR. The average metabolic rate over 22 h of the BN rats subjected to CR was reduced, whereas that of LE rats was increased slightly above the AL group. The respiratory quotient of BN rats wasdecreased with CR. Overall health of the CR LE group was significantly improved compared with t

Genetic susceptibility to mammary carcinogenesis in rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

1999-06-01

The Copenhagen (COP) rat strain has previously been shown to be genetically resistant to chemical induction of breast cancer, while Wistar/Furth (WF) and Fischer 344 (F344) animals are relatively susceptible. We have compared the carcinogenic response of these three strains of rats to N-methyl-N-nitrosourea (MNU) with that to {sup 60}Co gamma rays. High incidences of mammary carcinomas were induced by MNU in the F344 and WF rats (100%), whereas the COP strain proved resistant (11.8%). In contrast, radiation-induced mammary carcinomas in COP rats developed in a similar incidence (37.0%) to those in the F344 (22.6%) and WF (26.9%) strains. The low incidence of papillary carcinomas in MNU-treated COP rats appeared to be directly related to the COP genetic resistance controlled by the Mcs genes. Ionizing radiation did, however, induce papillary carcinomas in all the three strains of rats. These carcinomas were more differentiated than MNU-induced cancers with regard to the two mammary differentiation markers, rat milk fat globule membrane (R-MFGM) and {alpha}-smooth muscle actin ({alpha}-SMA). Furthermore, ionizing radiation but not MNU induced mammary adenomas in all three strains, especially in COP rats. Such adenomas had differentiation marker profiles similar to these of carcinomas induced by {sup 60}Co gamma rays. When transplanted into syngenic hosts, growth of adenomas was 17 {beta}-estradiol (E{sub 2})-dependent and they progressed to carcinomas. Furthermore, one microcarcinoma was observed to develop from adenoma tissue in a radiation-exposed COP rat. The findings suggest that radiation and chemical carcinogens are likely to induce mammary cancers through different pathways or from different cell populations. The induction of relatively high incidences of mammary carcinomas and adenomas by radiation in COP rats may correlate with the genetically modulated and highly differentiated physiological status of their mammary glands. (author)

Modifying factors in rat mammary gland carcinogenesis

International Nuclear Information System (INIS)

Shellabarger, C.J.

1975-01-01

The spontaneous incidence of mammary adenocarcinomas and mammary fibroadenomas in rats was found to be related to the strain of rat studied. Strains of rats that are sensitive to chemical carcinogens in regard to induced mammary neoplasia tend to be the same strains of rats that are sensitive to radiation. Methylcholantrene (MCA) and x-rays appeared to act in an additive fashion on the induction of mammary adenocarcinomas when they were given together. Lactating and older rats lose responsiveness to chemical carcinogens but do not lose responsiveness to radiation. Radiation appears to act in a scopal fashion in the induction of mammary neoplasia. Mammary neoplasia induction was not changed when low LET radiation was split into 2 equal fractions and high LET radiation was more effective than low LET radiation in inducing mammary neoplasia. It is suggested that DMBA can act as an initiator for the induction of mammary adenocarcinomas, that phorbol can act as a promotor, and that viruses may induce mammary neoplasia. Diethylstilbestrol (DES) and radiation appeared to act synergistically in the induction of mammary adenocarcinomas in one strain of rat but not in another strain. (U.S.)

Detection and Specific Enumeration of Multi-Strain Probiotics in the Lumen Contents and Mucus Layers of the Rat Intestine After Oral Administration.

Science.gov (United States)

Lee, Hee Ji; Orlovich, David A; Tagg, John R; Fawcett, J Paul

2009-12-01

Although the detection of viable probiotic bacteria following their ingestion and passage through the gastrointestinal tract (GIT) has been well documented, their mucosal attachment in vivo is more difficult to assess. In this study, we investigated the survival and mucosal attachment of multi-strain probiotics transiting the rat GIT. Rats were administered a commercial mixture of the intestinal probiotics Lactobacillus acidophilus LA742, Lactobacillus rhamnosus L2H and Bifidobacterium lactis HN019 and the oral probiotic Streptococcus salivarius K12 every 12 h for 3 days. Intestinal contents, mucus and faeces were tested 6 h, 3 days and 7 days after the last dose by strain-specific enumeration on selective media and by denaturing gradient gel electrophoresis. At 6 h, viable cells and DNA corresponding to all four probiotics were detected in the faeces and in both the lumen contents and mucus layers of the ileum and colon. Viable probiotic cells of B. lactis and L. rhamnosus were detected for 7 days and L. acidophilus for 3 days after the last dose. B. lactis and L. rhamnosus persisted in the ileal mucus and colon contents, whereas the retention of L. acidophilus appeared to be relatively higher in colonic mucus. No viable cells of S. salivarius K12 were detected in any of the samples at either day 3 or 7. The study demonstrates that probiotic strains of intestinal origin but not of oral origin exhibit temporary colonisation of the rat GIT and that these strains may have differing relative affinities for colonic and ileal mucosa.

A general protocol of ultra-high resolution MR angiography to image the cerebro-vasculature in 6 different rats strains at high field.

Science.gov (United States)

Pastor, Géraldine; Jiménez-González, María; Plaza-García, Sandra; Beraza, Marta; Padro, Daniel; Ramos-Cabrer, Pedro; Reese, Torsten

2017-09-01

Differences in the cerebro-vasculature among strains as well as individual animals might explain variability in animal models and thus, a non-invasive method tailored to image cerebral vessel of interest with high signal to noise ratio is required. Experimentally, we describe a new general protocol of three-dimensional time-of-flight magnetic resonance angiography to visualize non-invasively the cerebral vasculature in 6 different rat strains. Flow compensated angiograms of Sprague Dawley, Wistar Kyoto, Lister Hooded, Long Evans, Fisher 344 and Spontaneous Hypertensive Rat strains were obtained without the use of contrast agents. At 11.7T using a repetition time of 60ms, an isotropic resolution of up to 62μm was achieved; total imaging time was 98min for a 3D data set. The visualization of the cerebral arteries was improved by removing extra-cranial vessels prior to the calculation of maximum intensity projection to obtain the angiograms. Ultimately, we demonstrate that the newly implemented method is also suitable to obtain angiograms following middle cerebral artery occlusion, despite the presence of intense vasogenic edema 24h after reperfusion. The careful selection of the excitation profile and repetition time at a higher static magnetic field allowed an increase in spatial resolution to reliably detect of the hypothalamic artery, the anterior choroidal artery as well as arterial branches of the peri-amygdoidal complex and the optical nerve in six different rat strains. MR angiography without contrast agent can be utilized to study cerebro-vascular abnormalities in various animal models. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The effect of new probiotic strain Lactobacillus plantarum on counts of coliforms, lactobacilli and bacterial enzyme activities in rats exposed to N,N-dimethylhydrazine (chemical carcinogen

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Denisa Čokášová

2012-01-01

Full Text Available The aim of the present study was to evaluate the effect of the new probiotic strain Lactobacillus plantarum on chemically induced carcinogenesis in rats. Sprague dowley rats (n = 33 were divided into control and experimental groups and were fed a conventional laboratory diet. In the experimental group, rats were treated with the probiotic at the dose of 1 × 109 CFU (colony-forming units/ml. Two weeks after the beginning of the trial, N,N-dimethylhydrazine (chemical carcinogen injections were applied s.c. at the dose of 21 mg/kg b.w., 5 × weekly. At the end of the 8-month experimental period, faeces samples were taken from the rats and used for laboratory analysis. The counts of lactobacilli and coliforms and bacterial enzyme activity were determined. The probiotic strain L. plantarum as single species or in combination with oil (Lini oleum virginale decreased the count of total coliforms and increased lactobacilli in faeces of rats. Application of probiotic microorganisms significantly (P < 0.05 decreased the activities of bacterial enzymes (β-galactosidase and β-glucuronidase compared to the control group rats. The results of this study indicate that probiotic microorganisms could exert a preventive effect on colon carcinogenesis induced by N,N-dimethylhydrazine.

Novel polymorphisms within the Dlk1-Dio3 imprinted locus in rat: a putative genetic basis for strain-specific allelic gene expression

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Laura J Sittig

2012-12-01

Full Text Available The imprinted iodothyronine deiodinase-III (Dio3 thyroid hormone metabolizing gene exhibits paternal expression in most fetal tissues, yet exhibits aberrant, maternal expression in the hippocampus in F1 offspring of Sprague Dawley (SD x Brown Norway (BN rats. The maternal hippocampal expression is associated with lower Dio3 mRNA levels specifically in the hippocampus. Here, we tested the hypothesis that genetic polymorphisms between the SD and BN parent strains cause this aberrant allelic Dio3 expression and contribute to behavioral sequelae of higher thyroid hormone levels locally in the hippocampus, including anxiety-related behavior. We mapped and sequenced the Dio3 gene and several previously unmapped regions in the Dlk1-Dio3 locus that could regulate imprinting of the Dio3 gene. In the Dio3 promoter we identified four novel polymorphisms between the BN and SD strains. Next we took advantage of the fact that the Long Evans (LE strain exhibits identical polymorphisms as the SD strain in the region 5’ and including the Dio3 gene. By reciprocally crossing LE and BN strains we tested the relationship among Dio3 promoter region polymorphisms and Dio3 mRNA expression in the hippocampus. Aberrant strain-specific hippocampal Dio3 allelic expression replicated in the LE-BN reciprocal crosses, suggesting that hippocampal-specific imprinting of the Dio3 gene is not the result of a unique genetic or epigenetic characteristic of the SD rat strain, or a unique epistatic interaction between SD and BN. To our knowledge no other studies have reported a genetic x epigenetic interaction of genetic origin in the brain.

Pivotal Advance: Eosinophilia in the MES rat strain is caused by a loss-of-function mutation in the gene for cytochrome b(-245), alpha polypeptide (Cyba).

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Mori, Masayuki; Li, Guixin; Hashimoto, Maiko; Nishio, Ayako; Tomozawa, Hiroshi; Suzuki, Nobuyoshi; Usami, Shin-ichi; Higuchi, Keiichi; Matsumoto, Kiyoshi

2009-09-01

MES is a rat strain that spontaneously develops severe blood eosinophilia as a hereditary trait. Herein, we report that eosinophilia in MES rats is caused by a loss-of-function mutation in the gene for cytochrome b(-245), alpha polypeptide (Cyba; also known as p22(phox)), which is an essential component of the superoxide-generating NADPH oxidase complex. The MES rat has a deletion of four nucleotides, including the 5' splice donor GpT of intron 4 of the Cyba gene. As a consequence of the deletion, a 51-nucleotide sequence of intron 4 is incorporated into the Cyba transcripts. Leukocytes from the MES strain lack both CYBA protein and NADPH oxidase activity. Nevertheless, unlike patients with chronic granulomatous disease, who suffer from infections with pathogens due to similar genetic defects in NADPH oxidase, MES rats retain normal innate immune defense against Staphylococcus aureus infection. This is due to large quantities of peritoneal eosinophils in MES rats, which phagocytose and kill the bacteria. MES rat has a balance defect due to impaired formation of otoconia in the utricles and saccules. Eosinophilia of the MES rat was normalized by introduction of a normal Cyba transgene. The mechanisms by which impairment of NADPH oxidase leads to eosinophilia in the MES rat are elusive. However, our study highlights the essential role of NADPH oxidase in homeostatic regulation of innate immunity beyond conventional microbicidial functions.

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

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Jitender P Dubey

Full Text Available The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse.Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i. to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25% of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle.This study reevaluated

A microfabricated strain gauge array on polymer substrate for tactile neuroprostheses in rats

International Nuclear Information System (INIS)

Beygi, M; Mutlu, S; Güçlü, B

2016-01-01

In this study, we present the design, microfabrication and characterization of a tactile sensor system which can be used for sensory neuroprostheses in rats. The sensor system consists of an array of 2  ×  7 cells, each of which has a series combination of four strain gauges. Each group of four strain gauges is placed around a square membrane with a size of 2.5  ×  2.5 mm 2 . Unlike most common tactile sensors based on silicon substrates, we used 3D-printed polylactic acid as a substrate, because it is not brittle, and under local extremes, it would prevent the catastrophic failure of all cells. The strain gauges were fabricated by depositing and patterning a 50 nm thick aluminum (Al) film on a polyimide sheet with a thickness of 0.125 mm. Polydimethylsiloxane (PDMS) elastomer was bonded on the top surface of the PI membrane. The PDMS layer was prepared in two different thicknesses, 1.2 and 1.7 mm, to investigate its effect on the static response of the sensor. The sensitivity and the maximum allowable force, corresponding to the maximum deformation of 0.9 mm at the center of each cell, changed based on the thickness of the PDMS layer. Sensor cells operated linearly up to 3 N with an average sensitivity of 200 mΩ N −1 (0.7 Ω mm −1 ) for 1.2 mm thick PDMS. These values changed to 4 N and 70 mΩ N −1 (0.3 Ω mm −1 ), respectively, for 1.7 mm thick PDMS. The nonlinearity was less than 3%. The cells had low cross-talk (∼5 mΩ N −1 and 0.02 Ω mm −1 ) relative to the average sensitivity. Additionally, the dynamic response of the sensor was characterized at several frequencies by using a vibrotactile stimulation system previously designed for psychophysics experiments. The sensor was also tested inside the rat conditioning chamber to demonstrate the relevant signals in a tactile neuroprosthesis. (paper)

A microfabricated strain gauge array on polymer substrate for tactile neuroprostheses in rats

Science.gov (United States)

Beygi, M.; Mutlu, S.; Güçlü, B.

2016-08-01

In this study, we present the design, microfabrication and characterization of a tactile sensor system which can be used for sensory neuroprostheses in rats. The sensor system consists of an array of 2  ×  7 cells, each of which has a series combination of four strain gauges. Each group of four strain gauges is placed around a square membrane with a size of 2.5  ×  2.5 mm2. Unlike most common tactile sensors based on silicon substrates, we used 3D-printed polylactic acid as a substrate, because it is not brittle, and under local extremes, it would prevent the catastrophic failure of all cells. The strain gauges were fabricated by depositing and patterning a 50 nm thick aluminum (Al) film on a polyimide sheet with a thickness of 0.125 mm. Polydimethylsiloxane (PDMS) elastomer was bonded on the top surface of the PI membrane. The PDMS layer was prepared in two different thicknesses, 1.2 and 1.7 mm, to investigate its effect on the static response of the sensor. The sensitivity and the maximum allowable force, corresponding to the maximum deformation of 0.9 mm at the center of each cell, changed based on the thickness of the PDMS layer. Sensor cells operated linearly up to 3 N with an average sensitivity of 200 mΩ N-1 (0.7 Ω mm-1) for 1.2 mm thick PDMS. These values changed to 4 N and 70 mΩ N-1 (0.3 Ω mm-1), respectively, for 1.7 mm thick PDMS. The nonlinearity was less than 3%. The cells had low cross-talk (~5 mΩ N-1 and 0.02 Ω mm-1) relative to the average sensitivity. Additionally, the dynamic response of the sensor was characterized at several frequencies by using a vibrotactile stimulation system previously designed for psychophysics experiments. The sensor was also tested inside the rat conditioning chamber to demonstrate the relevant signals in a tactile neuroprosthesis.

Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

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Diego Lopes Mendes Barretti

Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model.

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Haldar, Lopamudra; Gandhi, D N

2016-07-01

To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1) was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2) and (T3) groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4) was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat) were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. The rats those (T2 and T3) received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (pBacillus spore counts as compared to the control group (T4) and the group fed only skim milk (T1). In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model

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Lopamudra Haldar

2016-07-01

Full Text Available Aim: To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. Materials and Methods: An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1 was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2 and (T3 groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4 was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. Results: The rats those (T2 and T3 received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (p<0.01 in fecal coliform counts and increase (p<0.05 in both fecal lactobacilli and Bacillus spore counts as compared to the control group (T4 and the group fed only skim milk (T1. In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. Conclusions: This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

TGF-mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar-Kyoto rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Leyssac, P P

1986-01-01

fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations...

The three-kidney rat

International Nuclear Information System (INIS)

Provoost, A.P.; Van Aken, M.

1984-01-01

In contrast to the numerous research into the adaption of renal function when nephons are lost, much less attention has been paid to the effects of an extra kidney. Through the availability of inbred rat strains, techniques to transplant rat kidneys, and methods to measure total and individual kidney function repeatedly in the same animal, it became possible to study the renal function in rats with three kidneys. Adult male rats of a highly inbred Wistar strain were used. Nine recipients of a third kidney (3-K) were compared with 5 sham operated control (2-K) rats. The total GFR, as measured by the plasma clearance of Cr-5l EDTA, was taken 1,3,6,9, and 15 weeks after operation. The contribution of each kidney to the total renal function was determined by a Tc-99m DTPA scan performed at weeks 10 and 16. After transplantation the total GFR of 3-K rats was, in general, not different from the value before transplantation or from that of 2-K rats. The lack of increase of the GFR of 3-K rats was not the result of a non-functioning graft

5-HT_2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains

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Klein, A B; Ultved, L; Adamsen, D

2014-01-01

The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat st...... difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction....

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver phosphoenolpyruvate carboxykinase (PEPCK) activity, glucose homeostasis and plasma amino acid concentrations in the most TCDD-susceptible and the most TCDD-resistant rat strains

Energy Technology Data Exchange (ETDEWEB)

Viluksela, M.; Pohjanvirta, R.; Tuomisto, J.T.; Tuomisto, J. (National Public Health Inst., Laboratory of Toxicology, Kuopio (Finland)); Unkila, M. (Department of Pharmacology and Toxicology, Univ. of Kuopio (Finland)); Stahl, B.U.; Rozman, K.K. (Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States) Section of Environmental Toxicology, GSF-Institut fuer Toxikologie, Neuherberg (Germany))

1999-08-01

Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of reduced gluconeogenesis by comparing dose-responses and time-courses of effects of TCDD on the activity of phosphoenolpyruvate carboxykinase (PEPCK) in liver, liver glycogen concentration as well as plasma concentrations of glucose and amino acids in both genders of TCDD-sensitive Long-Evans (L-E) rats and TCDD-resistant Han/Wistar (H/W) rats. A dose-dependent decrease in PEPCK activity was observed in H/W rats, but in L-E rats the activity was not decreased. However, TCDD impaired the strong increase in liver PEPCK activity observed in pair-fed controls of the L-E strain. Liver glycogen concentrations were severely decreased in L-E rats and moderately in H/W rats. This effect seems to be secondary to reduced feed intake, since a similar decrease was seen in pair-fed controls. Decreases in plasma glucose concentrations were also more profound in L-E rats than in H/W rats, but pair-fed controls were generally less affected. Circulating concentrations of amino acids were markedly increased in TCDD-treated L-E rats, which is likely to reflect increased mobilization of amino acids and their decreased metabolism in liver. Reduction of liver PEPCK activity cannot account for the sensitivity difference of these two strains of rats in terms of mortality. Nevertheless, the response of both strains of TCDD-treated rats regarding gluconeogenesis is different from that seen in pair-fed controls and suggesting that impairment of this pathway contributes to the development of the wasting syndrome. (orig.) With 7 figs., 2 tabs., 47 refs.

Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.

Science.gov (United States)

Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

2010-11-01

Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (∼IL-8) and IFN-γ when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-γ and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only

Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

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Herrera, Victoria L; Pasion, Khristine A; Tan, Glaiza A; Ruiz-Opazo, Nelson

2013-01-01

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

Dahl (S × R rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

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Victoria L Herrera

Full Text Available A quantitative trait locus (QTL linked with ability to find a platform in the Morris Water Maze (MWM was located on chromosome 17 (Nav-5 QTL using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02. The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

Differential response of rat strains to obesogenic diets underlines the importance of genetic makeup of an individual towards obesity.

Science.gov (United States)

Mn, Muralidhar; Smvk, Prasad; Battula, Kiran Kumar; Nv, Giridharan; Kalashikam, Rajender Rao

2017-08-22

Obesity, a multifactorial disorder, results from a chronic imbalance of energy intake vs. expenditure. Apart from excessive consumption of high calorie diet, genetic predisposition also seems to be equally important for the development of obesity. However, the role of genetic predisposition in the etiology of obesity has not been clearly delineated. The present study addresses this problem by selecting three rat strains (WNIN, F-344, SD) with different genetic backgrounds and exposing them to high calorie diets. Rat strains were fed HF, HS, and HFS diets and assessed for physical, metabolic, biochemical, inflammatory responses, and mRNA expression. Under these conditions: significant increase in body weight, visceral adiposity, oxidative stress and systemic pro-inflammatory status; the hallmarks of central obesity were noticed only in WNIN. Further, they developed altered glucose and lipid homeostasis by exhibiting insulin resistance, impaired glucose tolerance, dyslipidemia and fatty liver condition. The present study demonstrates that WNIN is more prone to develop obesity and associated co-morbidities under high calorie environment. It thus underlines the cumulative role of genetics (nature) and diet (nurture) towards the development of obesity, which is critical for understanding this epidemic and devising new strategies to control and manage this modern malady.

Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat.

Science.gov (United States)

Gheni, Ghupurjan; Yokoi, Norihide; Beppu, Masayuki; Yamaguchi, Takuro; Hidaka, Shihomi; Kawabata, Ayako; Hoshino, Yoshikazu; Hoshino, Masayuki; Seino, Susumu

2015-01-01

We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.

Ultrastructural changes in spermatogonia of Wistar strain rats following acute whole-body X-ray exposure

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Hrehorovsky, M; Horak, J [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1980-01-01

Changes in spermatogonia ultrastructure in rats of Wistar strain after single whole-body X-ray irradiation with 6.4 mC.kg/sup -1/, 25.8 mC.kg/sup -1/ and 51.6 mC.kg/sup -1/ respectively, were studied. Intracellular spaces were found between spermatogonia enlarged, nuclear membranes were bent, the pheripheral teritories of chromation were electronoptically denser, the morphology of nucleoli was changed, cytoplasm was vacuolised, mitochondria were damaged, the vacuolar dilatation of agranular endoplasmic reticulum was evident and electronoptically empty vacuoles near the Golgi complex occured 48 hours after single whole-body X-ray irradiation. Qualitative changes in the ultrastructure of individual types of spermatogonia after individual exposures were similar.

Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

International Nuclear Information System (INIS)

Herlin, Maria; Kalantari, Fereshteh; Stern, Natalia; Sand, Salomon; Larsson, Sune; Viluksela, Matti; Tuomisto, Jouni T.; Tuomisto, Jouko; Tuukkanen, Juha; Jaemsae, Timo; Lind, P. Monica; Hakansson, Helen

2010-01-01

Background: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). Objectives: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. Methods: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000 ng TCDD/kg bw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. Results: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain

Biochemical studies of the macromolecular matrix of long bones in the Op/Orl mutant rat strain

Energy Technology Data Exchange (ETDEWEB)

Moczar, E; Berenholc, S; Phan-Dinh-Tuy, B; Robert, A M

1978-01-01

The long bones of normal and Op/Orl mutant rats were incubated with /sup 14/C-glucose and fractionated by EDTA and urea extraction. The analytical results of the various extracts suggested an increase in structural glycoprotein content and a decrease in collagen solubility in the long bones of mutants. Significant differences were found in the organic matrix composition of male and female bones of the two strains. /sup 14/C-glucose incorporation was stronger in males than in females. The presence of a glycosaminoglycan different from the chondroitinesulfate was shown in males. Basic amino acid content (lysine, arginine, histidine) was clearly higher in the insoluble residue of male bones .

Biochemical studies of the macromolecular matrix of long bones in the Op/Orl mutant rat strain

International Nuclear Information System (INIS)

Moczar, E.; Berenholc, S.; Phan-Dinh-Tuy, B.; Robert, A.M.

1978-01-01

The long bones of normal and Op/Orl mutant rats were incubated with 14 C-glucose and fractionated by EDTA and urea extraction. The analytical results of the various extracts suggested an increase in structural glycoprotein content and a decrease in collagen solubility in the long bones of mutants. Significant differences were found in the organic matrix composition of male and female bones of the two strains. 14 C-glucose incorporation was stronger in males than in females. The presence of a glycosaminoglycan different from the chondroitinesulfate was shown in males. Basic amino acid content (lysine, arginine, histidine) was clearly higher in the insoluble residue of male bones

Wistar-Kyoto Female Rats Are More Susceptible to Develop Sugar Binging: A Comparison with Wistar Rats

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Helena Papacostas-Quintanilla

2017-05-01

Full Text Available The hedonic component of the feeding behavior involves the mesolimbic reward system and resembles addictions. Nowadays, the excessive consumption of sucrose is considered addictive. The Wistar-Kyoto (WKY rat strain is prone to develop anxiety and addiction-like behavior; nevertheless, a lack of information regarding their vulnerability to develop sugar binging-like behavior (SBLB and how it affects the reward system persist. Therefore, the first aim of the present study was to compare the different predisposition of two rat strains, Wistar (W and WKY to develop the SBLB in female and male rats. Also, we studied if the SBLB-inducing protocol produces changes in anxiety-like behavior using the plus-maze test (PMT and, analyzed serotonin (5-HT and noradrenaline (NA concentrations in brain areas related to anxiety and ingestive behavior (brain stem, hypothalamus, nucleus accumbens, and amygdala. Finally, we evaluated whether fluoxetine, a drug that has been effective in reducing the binge-eating frequency, body weight, and severity of binge eating disorder, could also block this behavior. Briefly, WKY and W female rats were exposed to 30% sucrose solution (2 h, 3 days/week for 4 weeks, and fed up ad libitum. PMT was performed between the last two test periods. Immediately after the last test where sucrose access was available, rats were decapitated and brain areas extracted for high-performance liquid chromatography analysis. The results showed that both W and WKY female and male rats developed the SBLB. WKY rats consumed more calories and ingested a bigger amount of sucrose solution than their W counterpart. This behavior was reversed by using fluoxetine, rats exposed to the SBLB-inducing protocol presented a rebound effect during the washout period. On female rats, the SBLB-inducing protocol induced changes in NA concentrations on WKY, but not on W rats. No changes were found in 5-HT levels. Finally, animals that developed SBLB showed increased

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

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Jere Lindén

2014-08-01

Full Text Available One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21, appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance.

Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

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Tadashi Okamura

2013-01-01

Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

Chronic vitamin A-enriched diet feeding regulates hypercholesterolaemia through transcriptional regulation of reverse cholesterol transport pathway genes in obese rat model of WNIN/GR-Ob strain

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Shanmugam M Jeyakumar

2016-01-01

Full Text Available Background & objectives: Hepatic scavenger receptor class B1 (SR-B1, a high-density lipoprotein (HDL receptor, is involved in the selective uptake of HDL-associated esterified cholesterol (EC, thereby regulates cholesterol homoeostasis and improves reverse cholesterol transport. Previously, we reported in euglycaemic obese rats (WNIN/Ob strain that feeding of vitamin A-enriched diet normalized hypercholesterolaemia, possibly through hepatic SR-B1-mediated pathway. This study was aimed to test whether it would be possible to normalize hypercholesterolaemia in glucose-intolerant obese rat model (WNIN/GR/Ob through similar mechanism by feeding identical vitamin A-enriched diet. Methods: In this study, 30 wk old male lean and obese rats of WNIN/GR-Ob strain were divided into two groups and received either stock diet or vitamin A-enriched diet (2.6 mg or 129 mg vitamin A/kg diet for 14 wk. Blood and other tissues were collected for various biochemical analyses. Results: Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized abnormally elevated plasma HDL-cholesterol (HDL-C levels in obese rats as compared to stock diet-fed obese groups. Further, decreased free cholesterol (FC and increased esterified cholesterol (EC contents of plasma cholesterol were observed, which were reflected in higher EC to FC ratio of vitamin A-enriched diet-fed obese rats. However, neither lecithin-cholesterol acyltransferase (LCAT activity of plasma nor its expression (both gene and protein in the liver were altered. On the contrary, hepatic cholesterol levels significantly increased in vitamin A-enriched diet fed obese rats. Hepatic SR-B1 expression (both mRNA and protein remained unaltered among groups. Vitamin A-enriched diet fed obese rats showed a significant increase in hepatic low-density lipoprotein receptor mRNA levels, while the expression of genes involved in HDL synthesis, namely, ATP-binding cassette protein 1 (ABCA1 and

Heart resistance to oxidative stress in rats of different genetic strains.

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Belkina, L M; Lakomkin, V L; Zhukova, A G; Kirillina, T N; Saltykova, V A; Sazontova, T G; Kapel'ko, V I

2004-09-01

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

Bloqueo de las crisis audiogénicas y del choque electroconvulsivo por la 2-fenil-4,4-bis-(hidroximetil-2-oxazolina Block of the audiogenic seizures and of the electroconvulsive shock by 2-phenyl-4, 4-bis-(hydroxymethyl-2-oxazoline

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Milena Díaz Molina

2004-12-01

Full Text Available Algunas aril-oxazolinas han sido descritas como sustancias activas sobre el sistema nervioso central, con efectos y aplicaciones diversas como depresoras, anestésicos, anticonvulsivos, etc. El presente trabajo se trazó como objetivo fundamental estudiar el posible efecto de la 2-fenil-4,4-bis (hidroximetil-2-oxazolina (OX obtenida por síntesis química bajo microondas, en 2 modelos experimentales de epilepsia: el choque electroconvulsivo por estimulación repetitiva en ratones y el de inducción de crisis convulsiva por estímulo audiogénico en el gerbo mongol. La dosis de 150 mg/kg de OX redujo el número de pulsos eléctricos necesarios para inducir la crisis tónica producida por el choque eléctrico, así como su duración. Esta misma dosis bloqueó las crisis inducidas por el estímulo audiogénico en el gerbo, y disminuyó significativamente su severidad (grados de crisis y ocurrencia. Estos resultados permiten afirmar que OX presenta un efecto antiepiléptico relacionado posiblemente con una inhibición de la sinapsis glutamatérgica en el hipocampo.Some aryl-oxazolines have been described as active substances on the central nervous system, with diverse effects and applications as depressants, anesthetics, anticonvulsants, etc. The purpose of the present paper is to study the possible effect of 2-phenyl-4,4-bis (hydroxymethyl-2-oxazoline (OX obtained by chemical synthesis under microwaves in 2 experimental models of epilepsy: the electroconvulsive shock by repetitive stimulation in mice and that of induction of convulsive seizures by audiogenic stimulus in gerbo mongol. The dose of 150 mg/kg of OX reduced the number of electric pulses, as well as its duration. This same dose blocked the seizures induced by audiogenic stimulus in gerbo and significantly reduced its severity (seizure degrees and occurrence. These reults allow to assert that OX present an antiepilectic effect possibly related to an inhibition of glutamatergic synapse in

Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

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Littman Dan R

2009-01-01

Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

Differences in tubuloglomerular feedback--oscillatory activity between spontaneously hypertensive and Wistar-Kyoto rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Leyssac, P P

1985-01-01

strains, oscillations could be elicited by free flow microperfusion with artificial tubular fluid. When furosemide was added to the artificial tubular fluid in a concentration of 0.1 mmol/l, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats...

Probiotics for experimental obesity prevention: focus on strain dependence and viability of composition.

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Kobyliak, Nazarii; Falalyeyeva, Tetyana; Beregova, Tetyana; Spivak, Mykola

2017-01-01

a comparative animal study of the efficacy of intermittent short-course administration of lyophilised single-, three-, and live multistrain probiotic on obesity. We included 70 rats divided into seven groups (n = 10 in each). Rats of group I were intact. Newborn rats of groups II-VII were injected with monosodium glutamate (MSG) (4 mg/g). Rats of group II (MSG-obesity group) were untreated. The group III-V received lyophilised monoprobiotics B. animalis VKL, B. animalis VKB, and L. casei IMVB-7280, respectively. Group VI received the mix of these three probiotic strains. Group VII was treated with multiprobiotic "Symbiter", which contains 14 live probiotic strains (Lactobacillus, Bifi-dobacterium, Propionibacterium, Acetobacter genera). Neonatal treatment with MSG caused stunted growth, which is why, despite the lack of weight gain dynamics and absence of significant food consumption rate and body weight changes at day 120, we noted the development of obesity in all MSG-obesity rats and in up to 20-70% after probiotic administration. Supplementation of probiotic composition, with preference to live strains, led to a significantly lower prevalence of obesity, and reduction of VAT weight and serum lipid levels as compared to single-strain probiotic. In our comparative single-strain analysis a trend towards more pronounced hypolipidaemic effect and VAT weight reduction was observed for lyophilised L. casei IMVB-7280 as compared to B. animalis VKL and VKB strains. Multistrain formed mutualistic interactions in mixtures and therefore able to share with different metabolites, affect differ-ent receptors and produced various of biologically active compounds which synergistic overall effect greater than the sum of the single effects.

Sexual dimorphism in hybrids rats.

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Garcia-Falgueras, Alicia; Pinos, Helena; Fernández, Rosa; Collado, Paloma; Pasaro, Eduardo; Segovia, Santiago; Guillamon, Antonio

2006-12-06

Laboratory rat strains descend from Wistar rats as a consequence of artificial selection. Previously we reported that the medial posterior division of the bed nucleus of the stria terminalis (BSTMP) was sexually dimorphic in Wistar and Long-Evans strains while the medial anterior division (BSTMA) and the locus coeruleus (LC) only showed sex differences in the ancestor Wistar strain. The lateral posterior division (BSTLP) was isomorphic in both strains. The present work studies the number of neurons in the BSTMP, BSTMA, BSTLP and LC of male and female Wistar and Long-Evans rats (F(0)) and their hybrid F(1) and F(2) generations. The BSTMP is sexually dimorphic in the F(0), F(1) and F(2) generations while sex differences in the LC are only seen in F(0) Wistar rats but not in the F(0) Long-Evans or the F(1) and F(2) hybrid generations. Sex differences in the BSTMA are seen in F(0) Wistar but not in F(0) Long-Evans rats and completely disappear in the F(2) generations. The number of neurons in the LC of both males and females decreased in heterozygotic individuals (F(1)) but increased in homozygotic (F(2)). However, the number of neurons in the BSTMP changes significantly over the generations, although the ratio of neurons (female/male) is stable and unaffected in homo- or heterozygosis. Thus, the mechanism that regulates the neuronal female/male ratio would be different from the one that controls the number of neurons. The facts that sex differences in the BSTMP are not affected by homo- or heterozygosis and that they are seen in several mammalian orders suggest the existence of a "fixed" type of brain sex differences in the Mammalia Class.

Constitutively reduced sensory capacity promotes better recovery after spinal cord-injury (SCI) in blind rats of the dystrophic RCS strain.

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Rink, Svenja; Bendella, Habib; Alsolivany, Kurdin; Meyer, Carolin; Woehler, Aliona; Jansen, Ramona; Isik, Zeynep; Stein, Gregor; Wennmachers, Sina; Nakamura, Makoto; Angelov, Doychin N

2018-01-01

We compared functional, electrophysiological and morphological parameters after SCI in two groups of rats Sprague Dawley (SD) rats with normal vision and blind rats from a SD-substrain "Royal College of Surgeons" (SD/RCS) who lose their photoreceptor cells after birth due to a genetic defect in the retinal pigment epithelium. For these animals skin-, intramuscular-, and tendon receptors are major available means to resolve spatial information. The purpose of this study was to check whether increased sensitivity in SD/RCS rats would promote an improved recovery after SCI. All rats were subjected to severe compression of the spinal cord at vertebra Th8, spinal cord segment Th10. Recovery of locomotion was analyzed at 1, 3, 6, 9, and 12 weeks after SCI using video recordings of beam walking and inclined ladder climbing. Five functional parameters were studied: foot-stepping angle (FSA), rump-height index (RHI) estimating paw placement and body weight support, respectively, number of correct ladder steps (CLS) assessing skilled hindlimb movements, the BBB-locomotor score and an established urinary bladder score (BS). Sensitivity tests were followed by electrophysiological measurement of M- and H-wave amplitudes from contractions of the plantar musculature after stimulation of the tibial nerve. The closing morphological measurements included lesion volume and expression of astro- and microglia below the lesion. Numerical assessments of BBB, FSA, BS, lesion volume and GFAP-expression revealed no significant differences between both strains. However, compared to SD-rats, the blind SD/RCS animals significantly improved RHI and CLS by 6 - 12 weeks after SCI. To our surprise the withdrawal latencies in the blind SD/RCS rats were longer and the amplitudes of M- and H-waves lower. The expression of IBA1-immunoreactivity in the lumbar enlargement was lower than in the SD-animals. The longer withdrawal latencies suggest a decreased sensitivity in the blind SD/RCS rats, which

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

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Schouenborg Jens

2008-05-01

Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

Probiotic properties of Lactobacillus strains isolated from Tibetan kefir grains.

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Yongchen Zheng

Full Text Available The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05 decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05 higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05 increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05 higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for

Probiotic Properties of Lactobacillus Strains Isolated from Tibetan Kefir Grains

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Zheng, Yongchen; Lu, Yingli; Wang, Jinfeng; Yang, Longfei; Pan, Chenyu; Huang, Ying

2013-01-01

The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB) isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH) activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD) rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05) decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05) higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05) increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05) higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for manufacturing

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

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Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

2010-04-06

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and

Effects of low-level laser therapy (LLLT) and diclofenac (topical and intramuscular) as single and combined therapy in experimental model of controlled muscle strain in rats.

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de Paiva Carvalho, Rodrigo Leal; Leal-Junior, Ernesto Cesar Pinto; Petrellis, Maria Carla; Marcos, Rodrigo Labat; de Carvalho, Maria Helena Catelli; De Nucci, Gilberto; Lopes-Martins, Rodrigo Alvaro Brandão

2013-01-01

Muscle injuries represent ca 30% of sports injuries and excessive stretching of muscle causes more than 90% of injuries. Currently the most used treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), however, in last years, low-level laser therapy (LLLT) is becoming an interesting therapeutic modality. The aim of this study was to evaluate the effect of single and combined therapies (LLLT, topical application of diclofenac and intramuscular diclofenac) on functional and biochemical aspects in an experimental model of controlled muscle strain in rats. Muscle strain was induced by overloading tibialis anterior muscle of rats. Injured groups received either no treatment, or a single treatment with topical or intramuscular diclofenac (TD and ID), or LLLT (3 J, 810 nm, 100 mW) 1 h after injury. Walking track analysis was the functional outcome and biochemical analyses included mRNA expression of COX-1 and COX-2 and blood levels of prostaglandin E2 (PGE2 ). All treatments significantly decreased COX-1 and COX-2 gene expression compared with injury group (P levels and walking track analysis (P topical and intramuscular diclofenac in treatment of muscle strain injury in acute stage. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Strain, Sex, and Open-Field Behavior: Factors Underlying the Genetic Susceptibility to Helplessness

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Padilla, Eimeira; Barrett, Douglas W.; Shumake, Jason D.; Gonzalez-Lima, F.

2009-01-01

Learned helplessness represents a failure to escape after exposure to inescapable stress and may model human psychiatric disorders related to stress. Previous work has demonstrated individual differences in susceptibility to learned helplessness. In this study, we assessed different factors associated with this susceptibility, including strain, sex, and open-field behavior. Testing of three rat strains (Holtzman, Long-Evans, and Sprague-Dawley) revealed that Holtzman rats were the most susceptible to helplessness. Holtzman rats not only had the longest escape latencies following inescapable shock, but also showed spontaneous escape deficits in the absence of prior shock when tested with a fixed-ratio 2 (FR2) running response. Moreover, when tested with fixed-ratio 1 (FR1) running—an easy response normally unaffected by helplessness training in rats—inescapable shock significantly increased the escape latencies of Holtzman rats. Within the Holtzman strain, we confirmed recent findings that females showed superior escape performance and therefore appeared more resistant to helplessness than males. However, regression and covariance analyses suggest that this sex difference may be explained by more baseline ambulatory activity among females. In addition, some indices of novelty reactivity (greater exploration of novel vs. familiar open-field) predicted subsequent helpless behavior. In conclusion, Holtzman rats, and especially male Holtzman rats, have a strong predisposition to become immobile when stressed which interferes with their ability to learn active escape responses. The Holtzman strain therefore appears to be a commercially available model for studying susceptibility to helplessness in males, and novelty-seeking may be a marker of this susceptibility. PMID:19428642

Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats.

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Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Ren, Zuojun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S; Katsumata, Tadayoshi; DeSimone, John A; Lyall, Vijay

2011-11-01

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure.

Strain differences in baroceptor reflex in adult Wistar Kyoto rats

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Vitor E. Valenti

2010-01-01

Full Text Available OBJECTIVES: A subset of normotensive Sprague-Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype. METHODS: Male Wistar Kyoto (WKY rats (16 weeks old were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP and heart rate (HR. Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP in response to a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, i.v. and a pressor dose of phenylephrine (PE, 8 µg/kg, i.v.. Rats were divided into four groups: 1 low bradycardic baroreflex (LB, baroreflex gain (BG between -1 and -2 bpm/mmHg tested with PE; 2 high bradycardic baroreflex (HB, BG < -2 bpm/mmHg tested with PE; 3 low tachycardic baroreflex (LT, BG between -1 and -2 bpm/mmHg tested with SNP and; 4 high tachycardic baroreflex (HT, BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05. RESULTS: Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP. CONCLUSION: There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

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Maryna Perepelyuk

Full Text Available Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

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Tufik Sergio

2007-03-01

Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role

Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

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Katherine M Ku

Full Text Available The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD, allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD and Long-Evans (LE, between the ages of postnatal day (PND 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii the testing environment may profoundly influence the expression of strain-specific social behavior and (iii simple, automated measures of sociability may not capture the complexities of rat social interactions.

Mesolimbic effects of the antidepressant fluoxetine in Holtzman rats, a genetic strain with increased vulnerability to stress

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Padilla, Eimeira; Shumake, Jason; Barrett, Douglas W.; Sheridan, Eva C.; Gonzalez-Lima, F.

2011-01-01

This is the first metabolic mapping study of the effects of fluoxetine after learned helplessness training. Antidepressants are the most commonly prescribed medications, but the regions underlying treatment effects in affectively disordered brains are poorly understood. We hypothesized the antidepressant action of fluoxetine would produce adaptations in mesolimbic regions after two weeks of treatment. We used Holtzman rats, a genetic strain showing susceptibility to novelty-evoked hyperactivity and stress-evoked helplessness, to map regional brain metabolic effects caused by fluoxetine treatment. Animals underwent learned helplessness, and subsequently immobility time was scored in the forced swim test (FST). On the next day, animals began receiving two weeks of fluoxetine (5 mg/kg/day) or vehicle and were retested in the FST at the end of drug treatment. Antidepressant behavioral effects of fluoxetine were analyzed using a ratio of immobility during pre- and post-treatment FST sessions. Brains were analyzed for regional metabolic activity using quantitative cytochrome oxidase histochemistry as in our previous study using congenitally helpless rats. Fluoxetine exerted a protective effect against FST-induced immobility behavior in Holtzman rats. Fluoxetine also caused a significant reduction in the mean regional metabolism of the nucleus accumbens shell and the ventral hippocampus as compared to vehicle-treated subjects. Additional networks affected by fluoxetine treatment included the prefrontal-cingulate cortex and brainstem nuclei linked to depression (e.g. habenula, dorsal raphe and interpeduncular nucleus). We concluded that corticolimbic regions such as the prefrontal-cingulate cortex, nucleus accumbens, ventral hippocampus and key brainstem nuclei represent important contributors to the neural network mediating fluoxetine antidepressant action. PMID:21376019

Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

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Miryala, C.S.J.; Hiegel, C.; Uphouse, L.

2012-01-01

Introduction The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT1A receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT1A receptors holds for other rat strains is not known. Aim The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT1A receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Main Outcome Measures Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC50 for inhibition of lordosis behavior was determined. Methods Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Results In both the intact and the hormonally-primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose-dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally-primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT1A receptor agonist. Conclusions Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT1A receptor agonist. Fluoxetine’s inhibition of female rat

Opioid modulation of GABA release in the rat inferior colliculus

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Forge Andrew

2004-09-01

Full Text Available Abstract Background The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication. Results Using a perfusion protocol we demonstrate that morphine can inhibit KCl-induced release of [3H]GABA from rat inferior colliculus slices. DAMGO ([D-Ala(2, N-Me-Phe(4, Gly(5-ol]-enkephalin but not DADLE ([D-Ala2, D-Leu5]-enkephalin or U69593 has the same effect as morphine indicating that μ rather than δ or κ opioid receptors mediate this action. [3H]GABA release was diminished by 16%, and this was not altered by the protein kinase C inhibitor bisindolylmaleimide I. Immunostaining of inferior colliculus cryosections shows extensive staining for glutamic acid decarboxylase, more limited staining for μ opiate receptors and relatively few neurons co-stained for both proteins. Conclusion The results suggest that μ-opioid receptor ligands can modify neurotransmitter release in a sub population of GABAergic neurons of the inferior colliculus. This could have important physiological implications in the processing of hearing information and/or other functions attributed to the inferior colliculus such as audiogenic seizures and aversive behaviour.

Opioid modulation of GABA release in the rat inferior colliculus

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Tongjaroenbungam, Walaiporn; Jongkamonwiwat, Nopporn; Cunningham, Joanna; Phansuwan-Pujito, Pansiri; Dodson, Hilary C; Forge, Andrew; Govitrapong, Piyarat; Casalotti, Stefano O

2004-01-01

Background The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication. Results Using a perfusion protocol we demonstrate that morphine can inhibit KCl-induced release of [3H]GABA from rat inferior colliculus slices. DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin) but not DADLE ([D-Ala2, D-Leu5]-enkephalin or U69593 has the same effect as morphine indicating that μ rather than δ or κ opioid receptors mediate this action. [3H]GABA release was diminished by 16%, and this was not altered by the protein kinase C inhibitor bisindolylmaleimide I. Immunostaining of inferior colliculus cryosections shows extensive staining for glutamic acid decarboxylase, more limited staining for μ opiate receptors and relatively few neurons co-stained for both proteins. Conclusion The results suggest that μ-opioid receptor ligands can modify neurotransmitter release in a sub population of GABAergic neurons of the inferior colliculus. This could have important physiological implications in the processing of hearing information and/or other functions attributed to the inferior colliculus such as audiogenic seizures and aversive behaviour. PMID:15353008

Restriction map of the single-stranded DNA genome of Kilham rat virus strain 171, a nondefective parvovirus

International Nuclear Information System (INIS)

Banerjee, P.T.; Rathrock, R.; Mitra, S.

1981-01-01

A physical map of Kilham rat virus strain 171 DNA was constructed by analyzing the sizes and locations of restriction endonuclease-generated fragments of the replicative-form viral DNA synthesized in vitro. BglI, KpnI, BamHI, SmaI, XhoI, and XorII did not appear to have any cleavage sites, whereas 11 other enzymes cleaved the genome at one to eight sites, and AluI generated more than 12 distinct fragments. The 30 restriction sites that were mapped were distributed randomly in the viral genome. A comparison of the restriction fragments of in vivo- and in vitro-replicated replicative-form DNAs showed that these DNAs were identical except in the size or configuration of the terminal fragments

ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

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Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

2009-01-01

Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

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Miloslava Hodúlová

Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

Identification of a Major Locus Contributing to Erythrocyte 2,3-Diphosphoglycerate Variability in Hooded (Long-Evans) Rats

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Noble, N. A.; Brewer, G. J.

1977-01-01

The erythrocyte glycolytic intermediate 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) play an important role in oxygen transport and delivery by binding to hemoglobin (Hb) and reducing its affinity for oxygen. Considerable quantitative variability in the levels of DPG and ATP exists in human populations and in a population of hooded (Long-Evans) rats we have studied. This paper presents the results of studies on the genetic component of DPG-level variation in an outbred population of hooded rats. Beginning with about 100 rats, a two-way selection experiment was initiated. Pairs of rats with the highest DPG levels were mated to produce a High-DPG rat strain and animals with the lowest DPG levels were mated to produce a Low-DPG strain. Mean DPG levels responded rapidly to selection and, from generation 3 on, the differences between strain means were highly significant. Ten High-DPG strain rats were intercrossed with 10 Low-DPG strain rats of generation 10 to produce an F1 generation in which the DPG levels were almost as high as those of High-DPG animals. This indicates partial dominance of High-DPG alleles. The F2 DPG-level distribution showed two distinct subpopulations. The high DPG subpopulation contained three times as many animals as the low DPG subpopulation. From these results and the statistical analyses performed, it was concluded that the DPG differences between strains were due to an allelic difference at one major locus, the allele carried by the High-DPG strain showing partial dominance over the allele carried by the Low-DPG strain. It appears that this locus may also effect ATP levels to a large extent and is polymorphic in hooded rat populations. Identification of this locus gives us a useful tool for studies of the physiological effects of DPG variability, as well as providing an example of a major gene effect in a quantitatively varying trait. PMID:863239

Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.

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Vogel, Heike; Kraemer, Maria; Rabasa, Cristina; Askevik, Kaisa; Adan, Roger A H; Dickson, Suzanne L

2017-06-15

Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib.

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Podratz, Jewel L; Kulkarni, Amit; Pleticha, Josef; Kanwar, Rahul; Beutler, Andreas S; Staff, Nathan P; Windebank, Anthony J

2016-03-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL/6J, DBA/2J, BALB/cJ, and C3H/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL/6J and Balb/cJ DRG-NOG was more sensitive to cisplatin than DBA/2J and C3H/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA/2J and C3H/H3J mice. C57BL/6J DRG-NOG was most sensitive and Balb/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat

NARCIS (Netherlands)

Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

2013-01-01

Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and

Effect of honey consumption on intestinal motility in male albino rats ...

African Journals Online (AJOL)

Summary: This study investigated the effects of honey on intestinal motility and transit using twenty (20) male albino rats of Wistar strain weighing 210-220g. The rats were randomly grouped into control and honey-fed (test) groups of ten (10) rats each. The control group was fed on normal rat chow ( Pfizer Company, Nigeria ) ...

Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains

DEFF Research Database (Denmark)

Fomsgaard, Luna; Moreno, Jose L; de la Fuente Revenga, Mario

2018-01-01

The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putativ...

Comprehensive behavioural analysis of Long Evans and Sprague-Dawley rats reveals differential effects of housing conditions on tests relevant to neuropsychiatric disorders.

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Karly M Turner

Full Text Available Genetic (G and environmental (E manipulations are known to alter behavioural outcomes in rodents, however many animal models of neuropsychiatric disorders only use a restricted selection of strain and housing conditions. The aim of this study was to examine GxE interactions comparing two outbred rat strains, which were housed in either standard or enriched cages. The strains selected were the albino Sprague-Dawley rat, commonly used for animal models, and the other was the pigmented Long Evans rat, which is frequently used in cognitive studies. Rats were assessed using a comprehensive behavioural test battery and included well-established tests frequently employed to examine animal models of neuropsychiatric diseases, measuring aspects of anxiety, exploration, sensorimotor gating and cognition. Selective strain and housing effects were observed on a number of tests. These included increased locomotion and reduced pre-pulse inhibition in Long Evans rats compared to Sprague Dawley rats; and rats housed in enriched cages had reduced anxiety-like behaviour compared to standard housed rats. Long Evans rats required fewer sessions than Sprague Dawley rats to learn operant tasks, including a signal detection task and reversal learning. Furthermore, Long Evans rats housed in enriched cages acquired simple operant tasks faster than standard housed Long Evans rats. Cognitive phenotypes in animal models of neuropsychiatric disorders would benefit from using strain and housing conditions where there is greater potential for both enhancement and deficits in performance.

Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.

Science.gov (United States)

Gass, N; Becker, R; Schwarz, A J; Weber-Fahr, W; Clemm von Hohenberg, C; Vollmayr, B; Sartorius, A

2016-12-06

Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.

Horizontal transfer of tet(M) and erm(B) resistance plasmids from food strains of Lactobacillus plantarum to Enterococcus faecalis JH2-2 in the gastrointestinal tract of gnotobiotic rats

DEFF Research Database (Denmark)

Jacobsen, Louise; Wilcks, Andrea; Hammer, Karin

2007-01-01

Two wild-type strains of Lactobacillus plantarum previously isolated from fermented dry sausages were analysed for their ability to transfer antibiotic resistance plasmids in the gastrointestinal tract. For this purpose, we used gnotobiotic rats as an in vivo model. Rats were initially inoculated......(2) CFU g(-1) faeces towards the end of the experiment. For erm(B)-TCs, the number was significantly higher and increased to c. 10(3) CFU g(-1) faeces. To our knowledge, this is the first study showing in vivo transfer of wild-type antibiotic resistance plasmids from L. plantarum to E. faecalis....

Differences in the duration of sedative and anxiolytic effects of desmethyldiazepam in two outbred Wistar strains

NARCIS (Netherlands)

van der Laan, J W; de Boer, S.F.; van der Gugten, J; de Groot, G

Different sensitivities to benzodiazepines have been described for various strains of both rats and mice suggesting that variations in biological features of the animals are responsible for these differences. Since all reports concern inbred strains, we studied two outbred Wistar strains which are

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

Science.gov (United States)

Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

2017-02-01

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The effects of immune modulation on plutonium dioxide lung carcinogenesis in the rat

International Nuclear Information System (INIS)

Nolibe, D.; Discour, M.; Masse, R.; Lafuma, J.

1979-01-01

After inhalation of radioactive particles only some rats developed lung tumors. It was interesting to see whether this was a random effect or the result of different individual susceptibilities. Among the possible individual differences, cell mediated mechanisms and genetic factors have been reported. The relationships between cancerogenesis and host immune status are tested on rats submitted to an inhalation of plutonium dioxide particles after depression by azathioprine, hydrocortisone or thymectomy. The effects of immuno stimulation by BCG are also studied. The influence of genetic factors is studied with the same protocol on two strains of Wistar rats outbred or inbred. The incidence, nature, size, extension and metastases of tumors are compared between the groups. Results give a good evidence that AZA treated rats and thymectomized rats have a greater incidence of spontaneous tumors. This effect is observed at different levels in the two strains of rats. According to strain used, immunodepression have no or weak enhancing effect on PuO 2 tumor induction, but significant effect of development of tumors is always observed. A shift towards bronchogenic type is also observed. BCG have also an enhancing effect on development of tumors and no protective effect on their incidence

Effect of Dietary Amorphophallus sp From East Java on LDL-C Rats (Rattus novergicus Wistar Strain

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Sri Widyarti

2011-06-01

Full Text Available One of indication of obesity is high LDL-C . Obesity has serious risk to health, it can cause heart disease and stroke. Effort to lower obesity using drugs have significant side effects such as insomnia, increased blood pressure, dry mouth and so forth. Therefore using natural products that contain glucomannan to reduce obesity and LDL-C is good choise. Glucomannan in the global market derived from Amorphophallus konjac. In this study, we used glucomannan from Amorphophallus endemic East Java to reduce fattened Wistar rats. Amorphophallus that used include Amorphophallus muelleri, A.variabilis (variant: Brongkos 32; Brongkos 5; Wonorejo, Brangsi and Amorphophallus campanulatus (Var Selopuro. Amorphophallus diet was given to white rats of Wistar strain that previously fattened using a mixture of cholesterol and lard, in addition to PARS (Chicken Feed Race Super as a basic food. Amorphophallus konjac was used as control. Measurement of LDL-C was conducted in four different time points, namely 1. Prior to dietary cholesterol, 2. 24 days after the dietary cholesterol, 3 11 days after Amorphophallus (+cholesterol diet, 4. 25 days after Amorphophallus (+cholesterol diet. The results showed that the diet of A.variabilis potentially lowered blood cholesterol levels for their respective 22.98%, 5.85% and 7.37% for consecutive variant Brongkos 32; Brongkos 5; Wonorejo. Diet from A.campanulatus and A.konjac had not been able to reduce cholesterol to the end of observation (25 days.

Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats

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Therese A. Kosten

2012-03-01

Full Text Available Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA axis activity. Yet, compared to Fischer 344 (F344 rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg from saline using a two-lever, food-reinforced (FR10 procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Science.gov (United States)

Belkina, L M; Popkova, E V; Lakomkin, V L; Kirillina, T N; Zhukova, A G; Sazontova, T G; Usacheva, M A; Kapel'ko, V I

2006-02-01

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.

Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus

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Saasha Le

2017-06-01

Full Text Available Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3—a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1. The mammary cancer susceptible Wistar Furth (WF strain was the recipient, and the mammary cancer resistant Copenhagen (Cop strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3. Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6. Human genetic variants with p values for association to breast cancer risk below 10−7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10−7 < p < 10−3 were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14—a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.

Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

International Nuclear Information System (INIS)

Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

1986-01-01

Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-β endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I 125 h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables

Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

Energy Technology Data Exchange (ETDEWEB)

Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

1986-01-20

Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

The rat as animal model in breast cancer research: a histopathological study of radiation- and hormone-induced rat mammary tumors

International Nuclear Information System (INIS)

Zwieten, M.J. van.

1984-01-01

One of the goals of this monograph is to present data on the frequency of mammary neoplasms following irradiation and/or hormone administration in intact and castrated female rats of three strains allowed to live their natural life spans. These data are intended to give an overview of the effects of radiation and hormonal manipulation on the mammary gland based on histological examination of necropsied rats and using standard morphological criteria for mammary tumors. The second goal of this monograph is to provide detailed histological descriptions of the mammary tumors found in the various experimental groups as well as in several groups of untreated control rats. The aims are to examine whether possible strain-related and treatment-related differences in morphology or growth patterns exist, as well as to define the pathogensis of radiation-induced rat mammary tumors through the study of early lesions. An attempt will be made to describe tumor characteristics which may be of comparative value in identifying tumor types (and their induction methods) useful as models for specific human breast neoplasms. A rat mammary tumor classification system reflecting the morphological features useful for comparative purposes is also presented. (Auth.)

Diethylene glycol-induced toxicities show marked threshold dose response in rats

Energy Technology Data Exchange (ETDEWEB)

Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

2015-02-01

Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats

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Miroslav Dinić

2018-01-01

Full Text Available The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11 to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.

Comparisons of Venezuelan encephalitis virus strains by hemagglutination-inhibition tests with chicken antibodies.

Science.gov (United States)

Scherer, W F; Pancake, B A

1977-01-01

Twenty strains of Venezuelan encephalitis (VE) virus inoculated intravenously in large doses into roosters produced hemagglutination-inhibition (HI) antibodies detectable in plasmas within 7 to 10 days. No signs of illness occurred, and there was no evidence of viral growth in tissues since blood concentrations of infectious virus steadily decreased after inoculation. HI antibodies in early plasmas were specific for VE virus and did not cross-react significantly with two other North American alphaviruses, eastern and western encephalitis viruses. VE virus strains could be distinquished by virus-dilution, short-incubation HI, but not by plasma-dilution neutralization tests, by using early rooster antibodies. The distinctions by HI test were similar with some strains to, but different with other strains from, those described by Young and Johnson with the spiny rat antisera used to establish their subtype classifications of VE virus (14, 28). Nevertheless, results of HI tests with rooster antibodies correlated with equine virulence, as did results with spiny rat antibodies, and distinguished the new strains of virus that appeared in Middle America during the VE outbreak of 1969 from preexisting strains. PMID:591629

Involvement of hepatic xenobiotic related genes in bromadiolone resistance in wild Norway rats, Rattus norvegicus (Berk.)

DEFF Research Database (Denmark)

Markussen, Mette Drude; Heiberg, Ann-Charlotte; Alsbo, Carsten

2007-01-01

To examine the role of xenobiotic relevant genes in bromadiolone resistance in wild Norway rats (Rattus norvegicus) we compared the constitutive liver gene expression and expression upon bromadiolone administration in bromadiolone resistant and anticoagulant susceptible female rats using a LNA...... expressed in resistant than susceptible rats upon bromadiolone exposure. To establish how bromadiolone affected xenobiotic gene expression in the two strains we compared bromadiolone expression profiles to saline profiles of both strains. Bromadiolone mediated significant up-regulation of Cyp2e1 and Cyp3a3...... expression in the resistant rats whereas the rodenticide conferred down-regulation of Cyp2e1, Cyp3a3 and Gpox1 and induction of Cyp2c12 expression in susceptible rats. Cyp2c13 and Cyp3a2 expression were markedly suppressed in both strains upon treatment. This suggests that xenobiotic relevant enzymes play...

Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

Science.gov (United States)

Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

1990-01-01

Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

Energy Technology Data Exchange (ETDEWEB)

Thanos, P.K.; Wang, G.; Thanos, P.K..; Kim, R.; Cho, J.; Michaelides, M.; Anderson, B.J.; Primeaux, S.D.; Bray, G.A.; Wang, G.-J.; Robinson, J.K.; Volkow, N.D.

2010-12-01

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.

Influence of Chloramphenicol and Amoxicillin on Rat Liver ...

African Journals Online (AJOL)

This study examined the effect of chloramphenicol and amoxicillin on liver microsomal enzymes Ca2+-ATPase and Glucose-6-Phosphatase (G-6-P) and lipid peroxidation in rats. Male Wistar strain rats weighing 120 – 195 g were divided into four groups. Group one, the control group, received physiological saline, group ...

Inferior ectopic pupil and typical ocular coloboma in RCS rats.

Science.gov (United States)

Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-08-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

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Ana Isabel Garcia Diaz

2016-04-01

Full Text Available The Wistar Kyoto (WKY rat and the spontaneously hypertensive (SHR rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN and metabolic syndrome, respectively. Novel transgenic (Tg strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP under the rat elongation factor 1 alpha (EF1a promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult brain and behaviour: Variants of learning, anxiety and volumetric estimates.

Science.gov (United States)

Keeley, R J; Trow, J; Bye, C; McDonald, R J

2015-07-15

Marijuana is one of the most highly used psychoactive substances in the world, and its use typically begins during adolescence, a period of substantial brain development. Females across species appear to be more susceptible to the long-term consequences of marijuana use. Despite the identification of inherent differences between rat strains including measures of anatomy, genetics and behaviour, no studies to our knowledge have examined the long-term consequences of adolescent exposure to marijuana or its main psychoactive component, Δ(9)-tetrahydrocannabinol (THC), in males and females of two widely used rat strains: Long-Evans hooded (LER) and Wistar (WR) rats. THC was administered for 14 consecutive days following puberty onset, and once they reached adulthood, changes in behaviour and in the volume of associated brain areas were quantified. Rats were assessed in behavioural tests of motor, spatial and contextual learning, and anxiety. Some tasks showed effects of injection, since handled and vehicle groups were included as controls. Performance on all tasks, except motor learning, and the volume of associated brain areas were altered with injection or THC administration, although these effects varied by strain and sex group. Finally, analysis revealed treatment-specific correlations between performance and brain volumes. This study is the first of its kind to directly compare males and females of two rat strains for the long-term consequences of adolescent THC exposure. It highlights the importance of considering strain and identifies certain rat strains as susceptible or resilient to the effects of THC. Copyright © 2015 Elsevier B.V. All rights reserved.

The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC

Science.gov (United States)

Johnson, K.R.; Zheng, Q.Y.; Weston, M.D.; Ptacek, L.J.; Noben-Trauth, K.

2010-01-01

The human ortholog of the gene responsible for audiogenic seizure susceptibility in Frings and BUB/BnJ mice (mouse gene symbol Mass1) recently was shown to underlie Usher syndrome type IIC (USH2C). Here we report that the Mass1frings mutation is responsible for the early onset hearing impairment of BUB/BnJ mice. We found highly significant linkage of Mass1 with ABR threshold variation among mice from two backcrosses involving BUB/BnJ mice with mice of strains CAST/EiJ and MOLD/RkJ. We also show an additive effect of the Cdh23 locus in modulating the progression of hearing loss in backcross mice. Together, these two loci account for more than 70% of the total ABR threshold variation among the backcross mice at all ages. The modifying effect of the strain-specific Cdh23ahl variant may account for the hearing and audiogenic seizure differences observed between Frings and BUB/BnJ mice, which share the Mass1frings mutation. During postnatal cochlear development in BUB/BnJ mice, stereocilia bundles develop abnormally and remain immature and splayed into adulthood, corresponding with the early onset hearing impairment associated with Mass1frings. Progressive base–apex hair cell degeneration occurs at older ages, corresponding with the age-related hearing loss associated with Cdh23ahl. The molecular basis and pathophysiology of hearing loss suggest BUB/BnJ and Frings mice as models to study cellular and molecular mechanisms underlying USH2C auditory pathology. PMID:15820310

Placental dysfunction in Suramin-treated rats: impact of maternal diabetes and effects of antioxidative treatment.

Science.gov (United States)

Nash, Peppi; Olovsson, Matts; Eriksson, Ulf J

2005-04-01

The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model. Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20. In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E. Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.

Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

OpenAIRE

Alam, Imranul; Koller, Daniel L.; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla

2011-01-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which ...

Comparing rat and rabbit embryo-fetal developmental toxicity ...

Science.gov (United States)

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n=283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects betwe

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

Science.gov (United States)

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright �

[Comparative evaluation of Leningrad-3 mumps vaccine virus neurovirulence in a neonatal rat model].

Science.gov (United States)

Ignat'ev, G M; Otrashevskaia, E V; Rubin, S A

2011-01-01

The neurovirulence and replication potential of several mumps virus strains, including Leningrad-3 mumps vaccine virus (FSUE SIC "Microgen", Russia) and wild type strains isolated in the Novosibirsk Region (Russia), were assessed in rat tests. The mean neurovirulence scores of the Leningrad-3 virus (mumps vaccine strains (usually ranging from 0 to 5). In general, the relative ability of the viruses to replicate in the rat brain tracked with their neurovirulence scores. These results indicate a low neurovirulence potential of the Leningrad-3 mumps vaccine virus for humans.

Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

International Nuclear Information System (INIS)

Landolt, R.; Arn, D.

1979-01-01

The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

Directory of Open Access Journals (Sweden)

Sarah M. DeNucci

2010-01-01

Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

Science.gov (United States)

Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

2012-04-01

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis

International Nuclear Information System (INIS)

Massa, P.T.; ter Meulen, V.; Fontana, A.

1987-01-01

In search of a phenotypic marker determining genetically controlled susceptibility to delayed-type hypersensitivity (DTH) reactions in the brain-in particular, experimental autoimmune encephalomyelitis (EAE)- the authors have compared the γ-interferon (IFN-γ) induction of Ia molecules on astrocytes and macrophages from rat and mouse strains that are susceptible or resistant to this disease. They focused on Ia expression because DTH reactions to self or foreign antigens are largely mediated by lymphocytes restricted by class II (Ia) antigens of the major histocompatibility complex (MHC). The data demonstrate that Lewis (fully susceptible) and Brown Norway (BN) (fully resistant) rats are very different in that Lewis astrocytes express much higher levels of Ia than BN astrocytes. Similar data were obtained from an analysis of EAE-susceptible and -resistant mouse strains (SJL and BALB/c, respectively), which suggest that this phenomenon may be universal and not limited to only one mammalian species. At least one gene responsible for Ia hyperinduction is located outside the rat RT-1 or the mouse MHC locus. Animals congenic at the RT-1 or MHC locus of the resistant strain but with background genes of the susceptible strain exhibit intermediate levels of Ia compared to fully resistant and susceptible rodents, which fits well with the reduced EAE susceptibility of these congenic animals. Furthermore, hyperinduction of Ia is astrocyte specific, since peritoneal macrophages of susceptible and resistant strains exhibit identical profiles of Ia induction. Thus, astrocyte Ia hyperinducibility may be a major strain- and tissue-specific factor that contributes to Ia-restricted DTH reactions in the brain

Frequent combination of antimicrobial multiresistance and extraintestinal pathogenicity in Escherichia coli isolates from urban rats (Rattus norvegicus) in Berlin, Germany.

Science.gov (United States)

Guenther, Sebastian; Bethe, Astrid; Fruth, Angelika; Semmler, Torsten; Ulrich, Rainer G; Wieler, Lothar H; Ewers, Christa

2012-01-01

Urban rats present a global public health concern as they are considered a reservoir and vector of zoonotic pathogens, including Escherichia coli. In view of the increasing emergence of antimicrobial resistant E. coli strains and the on-going discussion about environmental reservoirs, we intended to analyse whether urban rats might be a potential source of putatively zoonotic E. coli combining resistance and virulence. For that, we took fecal samples from 87 brown rats (Rattus norvegicus) and tested at least three E. coli colonies from each animal. Thirty two of these E. coli strains were pre-selected from a total of 211 non-duplicate isolates based on their phenotypic resistance to at least three antimicrobial classes, thus fulfilling the definition of multiresistance. As determined by multilocus sequence typing (MLST), these 32 strains belonged to 24 different sequence types (STs), indicating a high phylogenetic diversity. We identified STs, which frequently occur among extraintestinal pathogenic E. coli (ExPEC), such as STs 95, 131, 70, 428, and 127. Also, the detection of a number of typical virulence genes confirmed that the rats tested carried ExPEC-like strains. In particular, the finding of an Extended-spectrum beta-lactamase (ESBL)-producing strain which belongs to a highly virulent, so far mainly human- and avian-restricted ExPEC lineage (ST95), which expresses a serogroup linked with invasive strains (O18:NM:K1), and finally, which produces an ESBL-type frequently identified among human strains (CTX-M-9), pointed towards the important role, urban rats might play in the transmission of multiresistant and virulent E. coli strains. Indeed, using a chicken infection model, this strain showed a high in vivo pathogenicity. Imagining the high numbers of urban rats living worldwide, the way to the transmission of putatively zoonotic, multiresistant, and virulent strains might not be far ahead. The unforeseeable consequences of such an emerging public health

Frequent combination of antimicrobial multiresistance and extraintestinal pathogenicity in Escherichia coli isolates from urban rats (Rattus norvegicus in Berlin, Germany.

Directory of Open Access Journals (Sweden)

Sebastian Guenther

Full Text Available Urban rats present a global public health concern as they are considered a reservoir and vector of zoonotic pathogens, including Escherichia coli. In view of the increasing emergence of antimicrobial resistant E. coli strains and the on-going discussion about environmental reservoirs, we intended to analyse whether urban rats might be a potential source of putatively zoonotic E. coli combining resistance and virulence. For that, we took fecal samples from 87 brown rats (Rattus norvegicus and tested at least three E. coli colonies from each animal. Thirty two of these E. coli strains were pre-selected from a total of 211 non-duplicate isolates based on their phenotypic resistance to at least three antimicrobial classes, thus fulfilling the definition of multiresistance. As determined by multilocus sequence typing (MLST, these 32 strains belonged to 24 different sequence types (STs, indicating a high phylogenetic diversity. We identified STs, which frequently occur among extraintestinal pathogenic E. coli (ExPEC, such as STs 95, 131, 70, 428, and 127. Also, the detection of a number of typical virulence genes confirmed that the rats tested carried ExPEC-like strains. In particular, the finding of an Extended-spectrum beta-lactamase (ESBL-producing strain which belongs to a highly virulent, so far mainly human- and avian-restricted ExPEC lineage (ST95, which expresses a serogroup linked with invasive strains (O18:NM:K1, and finally, which produces an ESBL-type frequently identified among human strains (CTX-M-9, pointed towards the important role, urban rats might play in the transmission of multiresistant and virulent E. coli strains. Indeed, using a chicken infection model, this strain showed a high in vivo pathogenicity. Imagining the high numbers of urban rats living worldwide, the way to the transmission of putatively zoonotic, multiresistant, and virulent strains might not be far ahead. The unforeseeable consequences of such an emerging public

Air puff-induced 22-kHz calls in F344 rats.

Science.gov (United States)

Inagaki, Hideaki; Sato, Jun

2016-03-01

Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Intestinal T lymphocytes of different rat strains in immunotoxicity

NARCIS (Netherlands)

Bruder, M.C.; Spanhaak, S.; Bruijntjes, J.P.; Michielsen, C.P.P.C.; Vos, J.G.; Kuper, C.F.

1999-01-01

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes

Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats

DEFF Research Database (Denmark)

Lange, Martin; Qvortrup, Klaus; Svendsen, Ole Lander

2004-01-01

collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10...

Developmental exposure to an environmental PCB mixture delays the propagation of electrical kindling from the amygdala.

Science.gov (United States)

Bandara, Suren B; Sadowski, Renee N; Schantz, Susan L; Gilbert, Mary E

2017-01-01

Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to evaluate the effect of developmental exposure to an environmentally relevant PCB mixture on seizure susceptibility in the rat. Female Long-Evans rats were dosed orally with 0 or 6mg/kg/day of the PCB mixture dissolved in corn oil vehicle 4 weeks prior to mating and continued through gestation and up until postnatal day (PND) 21. On PND 21, pups were weaned, and two males from each litter were randomly selected for the kindling study. As adults, the male rats were implanted bilaterally with electrodes in the basolateral amygdala. For each animal, afterdischarge (AD) thresholds in the amygdala were determined on the first day of testing followed by once daily stimulation at a standard 200μA stimulus intensity until three stage 5 generalized seizures (GS) ensued. Developmental PCB exposure did not affect the AD threshold or total cumulative AD duration, but PCB exposure did increase the latency to behavioral manifestations of seizure propagation. PCB exposed animals required significantly more stimulations to reach stage 2 seizures compared to control animals, indicating attenuated focal (amygdala) excitability. A delay in kindling progression in the amygdala stands in contrast to our previous finding of increased susceptibility to brainstem-mediated audiogenic seizures in PCB-exposed animals in response to a an intense auditory stimulus. These seemingly divergent results are not unexpected given the distinct source, type, and mechanistic underpinnings of these different seizure models. A delay in epileptogenesis following focal amygdala stimulation may reflect a decrease in neuroplasticity following developmental PCB exposure consistent with reductions in use-dependent synaptic plasticity that

Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity

NARCIS (Netherlands)

Maassen, C.B.M.; Claassen, E.

2008-01-01

In this study we present new data showing strain-specific differences on the effect of commercially available probiotic drinks in an EAE rat autoimmune model for multiple sclerosis. In this particular model, we conclude that these drinks do not enhance but rather suppress the disease. We suggest

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

Science.gov (United States)

Womersley, Jacqueline S; Mpeta, Bafokeng; Dimatelis, Jacqueline J; Kellaway, Lauriston A; Stein, Dan J; Russell, Vivienne A

2016-06-17

Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains. Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague-Dawley strains but not in Wistar Kyoto rats. Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

Learned helplessness and social avoidance in the Wistar-Kyoto rat.

Science.gov (United States)

Nam, Hyungwoo; Clinton, Sarah M; Jackson, Nateka L; Kerman, Ilan A

2014-01-01

The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.

Learned helplessness and social avoidance in the Wistar-Kyoto rat

Directory of Open Access Journals (Sweden)

Hyungwoo eNam

2014-04-01

Full Text Available The Wistar-Kyoto (WKY rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs’ phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs’ behavior to that of Sprague-Dawley (SD, Wistar, and Spontaneously Hypertensive (SHR rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST. WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness. WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs’ behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e. neonatal handling that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.

From engineering to editing the rat genome.

Science.gov (United States)

Meek, Stephen; Mashimo, Tomoji; Burdon, Tom

2017-08-01

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). Despite this wealth of genetic and phenotypic diversity, the ability to manipulate and interrogate the genetic basis of existing phenotypes in rat strains and the methodology to generate new rat models has lagged significantly behind the advances made with its close cousin, the laboratory mouse. However, recent technical developments in stem cell biology and genetic engineering have again brought the rat to the forefront of biomedical studies and enabled researchers to exploit the increasingly accessible wealth of genome sequence information. In this review, we will describe how a breakthrough in understanding the molecular basis of self-renewal of the pluripotent founder cells of the mammalian embryo, embryonic stem (ES) cells, enabled the derivation of rat ES cells and their application in transgenesis. We will also describe the remarkable progress that has been made in the development of gene editing enzymes that enable the generation of transgenic rats directly through targeted genetic modifications in the genomes of zygotes. The simplicity, efficiency and cost-effectiveness of the CRISPR/Cas gene editing system, in particular, mean that the ability to engineer the rat genome is no longer a limiting factor. The selection of suitable targets and gene modifications will now become a priority: a challenge where

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

Science.gov (United States)

Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

International Nuclear Information System (INIS)

Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

1982-01-01

Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated

The Fischer 344 rat as a model of presbycusis.

Science.gov (United States)

Syka, Josef

2010-06-01

Due to the rising number of the aged human population all over the world, presbycusis is a phenomenon that deserves the increasing attention of the medical community as regards to prevention and treatment. This requires finding appropriate animal models for human presbycusis that will be useful in future experiments. Among the available rat strains, the Fischer 344 (F344) strain promises to serve as a model producing prompt and profound presbycusis. Hearing thresholds begin to increase in this strain during the first year of life; toward the end of the second year, the thresholds are very high. The threshold shifts progress independently in both ears. The rapid deterioration of distortion product otoacoustic emissions, with the majority of outer hair cells (OHC) being present and morphologically intact, is apparently produced by the disruption of prestin. The age-related changes within inner ear function are accompanied by deterioration of acoustical signal processing within central auditory system, mainly due to impaired GABA inhibition. The loss of GABA inhibition in old animals is expressed primarily in the inferior colliculus but is also present in the cochlear nuclei and the auditory cortex. Sound-evoked behavioral reactions are also impaired in old F344 rats. Taken together, the described characteristics of the aging F344 rat auditory system supports the idea that this strain may serve as a suitable model for studying the mechanisms of presbycusis, its prevention and treatment. Copyright 2009 Elsevier B.V. All rights reserved.

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

DEFF Research Database (Denmark)

Gibbs, Richard A; Weinstock, George M; Metzker, Michael L

2004-01-01

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering ove...

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

International Nuclear Information System (INIS)

Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

2000-01-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

2000-07-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Relationship between strains of tumor-bearing animals and the tumor affinity of /sup 169/Yb and /sup 67/Ga

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K; Ando, I; Ugiie, T

1975-02-01

It is well a well-known fact that ytterbium-169 is a strong bone seeking element. We have already reported that this element was concentrated in nonosseous tumor tissues and that its tumor affinity was stronger than that of gallium-67 in our previous experiment using Yoshida sarcoma-bearing rats. Ytterbium-169 citrate and gallium-67 citrate were compared in four strains of tumor-bearing rats and mice. The uptake rate of ytterbium-169 in tumor tissues was much larger than that of gallium-67 in Ehrlich cancer-bearing mice, but these values of ytterbium-169 were slightly smaller than those of gallium-67 in Yoshida sarcoma-bearing rats, Walker carcinosarcoma 256-bearing rats and sarcoma 180-bearing mice. Tumor to organ ratios of ytterbium-169, which were most important for tumor scanning agents, were much larger than those of gallium-67 in all four strains except for the tumor to bone ratio of ytterbium-169. From the above-described facts, it was shown that ytterbium-169 citrate had a stronger tumor affinity than did gallium-67 citrate and that the tumor affinity of ytterbium-169 citrate was similar in each of these four strains of tumor-bearing animals.

Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

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Giulia eCuria

2013-04-01

Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

Morphological study on dental caries induced in WBN/KobSlc rats (Rattus norvegicus) fed a standard laboratory diet.

Science.gov (United States)

Fukuzato, Yoko; Matsuura, Tetsuro; Ozaki, Kiyokazu; Matsuura, Masahiro; Sano, Tomoya; Nakahara, Yutaka; Kodama, Yasushi; Nakagawa, Akihito; Okamura, Sumie; Suido, Hirohisa; Torii, Kayo; Makino, Taketoshi; Narama, Isao

2009-10-01

In our previous studies, WBN/KobSlc was characterized as a rat strain in which only males began to develop pancreatitis, and then presented with diabetic symptoms. In the course of studying their pancreatic inflammation, we detected molar caries in prediabetic males feeding on a standard diet (CRF-1) widely used for experimental animals. The purpose of this study is to confirm whether the WBN/KobSlc strain is caries-susceptible to the diet reported to be non-cariogenic, and to examine the effect of a prediabetic condition on their dental caries. For a morphological study, 25 male WBN/KobSlc rats aged 3.2-7.8 months and 24 females of the same strain aged 3.3-6.6 months were used, along with 10 males and 10 females of 8.2-month-old F344 rats. Marked dental caries were detected in the mandibular molars of male and female WBN/KobSlc rats regardless of pancreatitis, although no similar changes were observed in any teeth of the F344 strain fed the same diet. Soft X-ray examination revealed that the caries began in the crown and progressed horizontally and vertically, and that a severe radiolucent lesion extensively expanded to the entire crown, corresponding to a macroscopically deleted molar. The caries had gradually developed mainly in the second mandibular molar from more than 3.5 months of age, while none were seen in any rats before that time. The WBN/KobSlc rats were caries-susceptible even to the standard laboratory diet, and pancreatitis was not directly associated with the onset of dental caries in this strain.

Strain differences in ethanol preference and reinforced behaviour: a comparison of two-bottle choice and operant self-administration paradigms.

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Wilson, A W; Neill, J C; Costall, B

1997-02-01

An animal's volitional consumption of ethanol may be influenced by both genetic and environmental factors. In addition, genetic control of ethanol intake may depend on the test paradigm used. In the present study, performance for, and intake of ethanol in a limited access oral operant paradigm, and preference for ethanol in a two-bottle free choice test in the home-cage were compared in female rats of the heterogeneous Sprague Dawley (SD) and inbred Lewis strains. A smaller proportion of SD rats reached criterion on the self-administration task (four of 10 SD vs eight of 10 Lewis), but those SD rats that did achieve criterion maintained higher levels of responding and greater ethanol intake, relative to the Lewis strain, in the operant self-administration paradigm. Additionally, SD but not Lewis rats exhibited increased locomotor activity and an increase in performance for ethanol compared with water. In marked contrast, Lewis rats exhibited a greater preference for 10% ethanol over water in the two-bottle choice test compared with the SD strain, which preferred water to ethanol. These results suggest that both genotype and test paradigm are involved in the extent to which ethanol serves as a positive reinforcer and that unlike two-bottle choice preference tests, self-administration studies are more highly predictive of the reinforcing properties of ethanol.

Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

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Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

2012-11-01

Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats.

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Plaza-Diaz, Julio; Gomez-Llorente, Carolina; Abadia-Molina, Francisco; Saez-Lara, Maria Jose; Campaña-Martin, Laura; Muñoz-Quezada, Sergio; Romero, Fernando; Gil, Angel; Fontana, Luis

2014-01-01

We have previously described the safety and immunomodulatory effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 in healthy volunteers. The scope of this work was to evaluate the effects of these probiotic strains on the hepatic steatosis of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker-Lepr(fa/fa) rats received one of three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An additional group of Zucker-lean+/fa rats received a placebo for 30 days. No alterations in intestinal histology, in the epithelial, lamina propria, muscular layers of the ileal or colonic mucosa, or the submucosae, were observed in any of the experimental groups. Triacylglycerol content decreased in the liver of Zucker-Lepr(fa/fa) rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve and L. paracasei. Likewise, the area corresponding to neutral lipids was significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa) rats that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa) rats exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon administration of placebo for 30 days. In contrast, all four groups of obese Zucker-Lepr(fa/fa) rats that received LAB strains exhibited serum LPS concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-α levels decreased in the Zucker-Lepr(fa/fa) rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Lepr(fa/fa) rats. In conclusion, the probiotic strains reduced hepatic steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in obese Zucker rats.

Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats.

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Julio Plaza-Diaz

Full Text Available We have previously described the safety and immunomodulatory effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 in healthy volunteers. The scope of this work was to evaluate the effects of these probiotic strains on the hepatic steatosis of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker-Lepr(fa/fa rats received one of three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An additional group of Zucker-lean+/fa rats received a placebo for 30 days. No alterations in intestinal histology, in the epithelial, lamina propria, muscular layers of the ileal or colonic mucosa, or the submucosae, were observed in any of the experimental groups. Triacylglycerol content decreased in the liver of Zucker-Lepr(fa/fa rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve and L. paracasei. Likewise, the area corresponding to neutral lipids was significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa rats that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa rats exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon administration of placebo for 30 days. In contrast, all four groups of obese Zucker-Lepr(fa/fa rats that received LAB strains exhibited serum LPS concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-α levels decreased in the Zucker-Lepr(fa/fa rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Lepr(fa/fa rats. In conclusion, the probiotic strains reduced hepatic steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in obese Zucker rats.

Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats

DEFF Research Database (Denmark)

Hossaini, Alireza; Dalgaard, Majken; Vinggaard, Anne

2003-01-01

to vehicle or 400 mg/kg bw of 4-tert-octylphenol administrated orally by gavage. Estradiol benzoate, at a dose of 40 mug/kg bw, was used as positive control agent. Treatment with estradiol benzoate decreased serum levels of testosterone, LH, FSH, inhibin and increased prolactin. Additionally, estradiol...... benzoate decreased the weight of all investigated reproductive organs, decreased sperm production and increased seminiferous tubular degeneration in both strains. More progressive effects on testis weight and histopathology were observed in the Fischer rats. Oral administration of octylphenol at 400 mg....../kg bw to both rat strains increased prolactin levels but had no effect on LH, FSH, testosterone or inhibin. In the octylphenol-treated Fischer rats the weights of the seminal vesicles and the levator ani/bulbocavernosus muscle were significantly decreased, whereas only the levator ani...

Multiple [3H]imipramine binding sites in brains of male and female Fawn-Hooded and Long-Evans rats

International Nuclear Information System (INIS)

Ieni, J.R.; Zukin, S.R.; Praag, H.M. van; Tobach, E.; Barr, G.A.

1985-01-01

Comparisons of high- and low-affinity [ 3 H]imipramine binding to whole brain homogenates from adult male and female rats of the Fawn-Hooded and Long-Evans strains were performed. Most strikingly, no significant differences were observed between the two strains in any of the binding parameters, indicating that brain [ 3 H]imipramine binding sites, which may be related to the serotonergic uptake process, appear normal in a strain of rats with serotonin platelet storage pool disease. However, a significant sex difference in high- but not low-affinity whole brain [ 3 H]imipramine Bsub(max) values was observed, with females of both strains having higher densities than males. (Auth.)

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Gulati, A.; Bhargava, H.N.

1990-01-01

The binding of [ 3 H] DAMGO, a highly selective ligand for μ-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [ 3 H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B max value) and apparent dissociation constant (K d value) of [ 3 H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B max value of [ 3 H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K d values in the two strains did not differ. On the other hand, the B max value of [ 3 H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K d values in the two strains were similar

Usefulness of real-time elastography strain ratio in the assessment of bile duct ligation-induced liver injury and the hepatoprotective effect of chitosan: an experimental animal study.

Science.gov (United States)

Dudea, Marina; Clichici, Simona; Olteanu, Diana Elena; Nagy, Andras; Cucoş, Maria; Dudea, Sorin

2015-01-01

The purpose of the study described here was to evaluate the usefulness of the elastographic strain ratio in the assessment of liver changes in an experimental animal setting and the hepatoprotective effects of chitosan. Ultrasonography and Strain Ratio calculation were performed before and after bile duct ligation (BDL) in three groups of Wistar albino rats (n = 10 animals per group): (i) rats subjected to bile duct ligation only; (ii) rats subjected to bile duct ligation and administered chitosan for 14 d; (iii) rats subjected to bile duct ligation and administered chitosan for 7 d. The results were compared with the laboratory data and pathologic findings. Strain ratios revealed an increase in liver stiffness after bile duct ligation (p liver response to injury. To the best of our knowledge, this is the first study reporting on the usefulness of the sonoelastographic liver-to-kidney strain ratio in assessing the effects of experimentally induced liver lesions. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ouabain binding to cultured vascular smooth muscle cells of the spontaneously hypertensive rat

International Nuclear Information System (INIS)

Hopp, L.; Khalil, F.; Tamura, H.; Kino, M.; Searle, B.M.; Tokushige, A.; Aviv, A.

1986-01-01

The binding of ouabain and K + to the Na + pump were analyzed in serially passed cultured vascular smooth muscle cells (VSMCs) originating from spontaneously hypertensive (SH) Wistar-Kyoto (WKY), and American Wistar (W) rats. The techniques have utilized analyses of displacement of [ 3 H]ouabain by both unlabeled ouabain and K + from specific binding sites on the VSMCs. The authors have found that 1) each of the VSMC preparations from the three rat strains appeared to demonstrate one population of specific ouabain receptors (Na + pumps); 2) the number of Na + pump units of both the SH and WKY rats was significantly lower than the number of Na + pump units of W rat VSMCs; 3) the equilibrium dissociation constant values (μM) for ouabain in VSMCs of SH and WKY rats were similar but were significantly higher than that of VSMCs derived from W rats; and 4) among the VSMCs originating from the three rat strains, the apparent equilibrium dissociation constant value for K + (mM) was the lowest in those of the SH rat compared with VSMCs of the WKY rat and W rat. Previous studies have demonstrated increased passive Na + and K + transport rate constants of SH rat VSMCs compared with either W or WKY rat cells. These findings suggest the possibility of higher permeabilities of the SH cells. They propose that the combined effect of a low number of Na + pump units with higher permeabilities to Na + and K + predisposes VSMCs of the SH rat to disturbances in their cellular ionic regulation. These genetic defects, if they occur in vivo, may lead to an increase in the vascular tone

Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

Science.gov (United States)

Vollmayr, Barbara; Bachteler, Daniel; Vengeliene, Valentina; Gass, Peter; Spanagel, Rainer; Henn, Fritz

2004-04-02

Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

Persistence of Bacillus thuringiensis bioinsecticides in the gut of human-flora-associated rats

DEFF Research Database (Denmark)

Wilcks, Andrea; Hansen, Bjarne Munk; Hendriksen, Niels Bohse

2006-01-01

The capability of two bioinsecticide strains of Bacillus thuringiensis (ssp. israelensis and ssp. kurstaki) to germinate and persist in vivo in the gastrointestinal tract of human-flora-associated rats was studied. Rats were dosed either with vegetative cells or spores of the bacteria for 4 conse...

Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

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Shin-ichiro Katsuda

2014-01-01

Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

Hepatic expression of spermatogenic genes and their transiently remarkable downregulations in Wistar-Kyoto rats in response to lead-nitrate administration: strain-difference in the gene expression patterns.

Science.gov (United States)

Nemoto, Kiyomitsu; Ito, Sei; Yoshida, Chiaki; Miyata, Misaki; Kojima, Misaki; Degawa, Masakuni

2011-06-01

Administration of lead ion (Pb) to rats and mice affects hepatic functions such as the induction of hepatic cell proliferation and upregulation of cholesterol biosynthesis. To identify the genes for which expression changes in response to Pb-administration, we analyzed hepatic gene expression patterns in stroke-prone spontaneously hypertensive rat (SHRSP), its normotensive control, Wistar-Kyoto rat (WKY), and Spraque-Dawley (SD) rat strains, 3, 6, and 12 hr later after single i.v. injection of lead nitrate (LN) at a dose of 100 µmol using a DNA microarray technique. The data analysis demonstrated that the expression of a great number of genes was transiently and remarkably downregulated 3 hr after LN-injection, and then recovered to control levels only in LN-injected WKY. These normal hepatic expression levels in WKY and SHRSP were much higher than those in SD rats. Furthermore, most of these genes were ones thought to be expressed specifically in the spermatids and/or testes; i.e. genes encoding protamin 1, transition protein 1, and transition protein 2. These findings suggest that the regulation system common to expression of all of these genes could be a target site of Pb-toxic action, at least, in the liver of WKY, and that this system might be similar to the system essential for spermatogenesis, especially spermiogenesis, in the testis. In addition, it appears that clarifying the cause of the difference between the systems of WKY and SHRSP might aid in identifying the pathologic genes in SHRSP. Finally, it will be an important to clarify how the products of the genes related to spermatogenesis, including spermiogenesis, are functional in the livers of WKY and SHRSP.

Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

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Lucie Šedová

Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

Ept7 influences estrogen action in the pituitary gland and body weight of rats.

Science.gov (United States)

Kurz, Scott G; Dennison, Kirsten L; Samanas, Nyssa Becker; Hickman, Maureen Peters; Eckert, Quincy A; Walker, Tiffany L; Cupp, Andrea S; Shull, James D

2014-06-01

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

1990-01-01

The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

Dissociation between spontaneously hypertensive (SHR) andWistar–Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a Visual Stimulus Position Discrimination Task

Energy Technology Data Exchange (ETDEWEB)

Thanos, P.K.

2009-10-08

The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at three different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.

Genetic analysis of the porcine group B rotavirus NSP2 gene from wild-type Brazilian strains

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K.C. Médici

2010-01-01

Full Text Available Group B rotaviruses (RV-B were first identified in piglet feces, being later associated with diarrhea in humans, cattle, lambs, and rats. In human beings, the virus was only described in China, India, and Bangladesh, especially infecting adults. Only a few studies concerning molecular analysis of the RV-B NSP2 gene have been conducted, and porcine RV-B has not been characterized. In the present study, three porcine wild-type RV-B strains from piglet stool samples collected from Brazilian pig herds were used for analysis. PAGE results were inconclusive for those samples, but specific amplicons of the RV-B NSP2 gene (segment 8 were obtained in a semi-nested PCR assay. The three porcine RV-B strains showed the highest nucleotide identity with the human WH1 strain and the alignments with other published sequences resulted in three groups of strains divided according to host species. The group of human strains showed 92.4 to 99.7% nucleotide identity while the porcine strains of the Brazilian RV-B group showed 90.4 to 91.8% identity to each other. The identity of the Brazilian porcine RV-B strains with outer sequences consisting of group A and C rotaviruses was only 35.3 to 38.8%. A dendrogram was also constructed to group the strains into clusters according to host species: human, rat, and a distinct third cluster consisting exclusively of the Brazilian porcine RV-B strains. This is the first study of the porcine RV-B NSP2 gene that contributes to the partial characterization of this virus and demonstrates the relationship among RV-B strains from different host species.

Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

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Nukman Moeloek

2009-11-01

Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

Effects of halothane-nitrous oxide inhalation anesthesia and Inactin on overall renal and tubular function in Sprague-Dawley and Wistar rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Christensen, P; Leyssac, P P

1982-01-01

Real function, plasma renin concentration (PRC) and prostaglandin (PG) excretion rate was studied in groups of Sprague-Dawley (SPRD) and Wistar (WIST) rats anesthetized with either Halothane-N2O or Inactin. Conscious rats were used as controls. A. In Halothane-N2O anesthesia inulin clearance (CIN...... anesthesia indicating that the proximal luminal diameter was constant and independent of CIN. B. Inactin anesthesia CIN was similarly reduced but APR was more depressed (by about 35%). RPF and solute excretion rate decreased only in SPRD rats, while urine flow was significantly reduced in both strains. 1/OT...... prepared rats are more severely depressed by Inactin than by Halothane-N2O anesthesia. The gas anesthesia is equally well tolerated by both strains of rats....

Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer.

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Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S

2013-08-01

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.

Whole-Genome Sequences of DA and F344 Rats with Different Susceptibilities to Arthritis, Autoimmunity, Inflammation and Cancer

Science.gov (United States)

Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A.; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S.

2013-01-01

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease. PMID:23695301

Prophage lambda induction (Inductest) of blood of rats fed irradiated spices

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Farkas, J; Andrassy, E [Koezponti Elelmiszeripari Kutato Intezet, Budapest (Hungary)

1981-01-01

Lysogenic Escherichia coli K12 strains Nos. GY 5023: envA uvr/sup +/ (lambda) and GY 5027: envA uvrB (lambda) were used as test organisms and E.coli strain No. GY 4015 as the indicator to investigate prophage induction (Inductest) of blood samples of CFY rats fed with black pepper and spice mixture treated with gamma radiation. The dose levels applied for the irradiation of spices were 0.5 and 15 kGy. In the rat feed, the applied concentration of ground black pepper was 3.5%, and that of the spice mixture (: mild paprika, black pepper, allspice, coriander, marjoram, cumin and nutmeg) was 25%. Blood samples were taken for prophage induction after six days' feeding with the tested diet. Tests with pepper were performed both within two weaks after irradiation and again after 90 days of storage following irradiation, while with the spice mixture, Inductest was performed with the blood of rats fed with a spice mixture irradiated 90 days before the start of the feeding test. Neither the blood of rats fed with irradiated pepper nor that of rats fed with irradiated spice mixture did increase, to a statistically significant degree, the occurrence of prophage induction as compared with blood samples of rats fed with a diet containing untreated spices or with commercial rat feed. In agreement with earlier microbial mutagenicity tests performed with extracts of irradiated spices and urine of rats fed with irradiated spices, neither did the present results indicate that spices irradiated with 5 and 15 kGy or their metabolites would be of DNA-modofying potential.

Prophage lambda induction (Inductest) of blood of rats fed irradiated spices

International Nuclear Information System (INIS)

Farkas, J.; Andrassy, E.

1981-01-01

Lysogenic Escherichia coli K12 strains Nos. GY 5023: envA uvr + (lambda) and GY 5027: envA uvrB (lambda) were used as test organisms and E.coli strain No. GY 4015 as the indicator to investigate prophage induction (Inductest) of blood samples of CFY rats fed with black pepper and spice mixture treated with gamma radiation. The dose levels applied for the irradiation of spices were 0.5 and 15 kGy. In the rat feed, the applied concentration of ground black pepper was 3.5%, and that of the spice mixture (: mild paprika, black pepper, allspice, coriander, marjoram, cumin and nutmeg) was 25%. Blood samples were taken for prophage induction after six days' feeding with the tested diet. Tests with pepper were performed both within two weaks after irradiation and again after 90 days of storage following irradiation, while with the spice mixture, Inductest was performed with the blood of rats fed with a spice mixture irradiated 90 days before the start of the feeding test. Neither the blood of rats fed with irradiated pepper nor that of rats fed with irradiated spice mixture did increase, to a statistically significant degree, the occurrence of prophage induction as compared with blood samples of rats fed with a diet containing untreated spices or with commercial rat feed. In agreement with earlier microbial mutagenicity tests performed with extracts of irradiated spices and urine of rats fed with irradiated spices, neither did the present results indicate that spices irradiated with 5 and 15 kGy or their metabolites would be of DNA-modofying potential. (author)

Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

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Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

2015-03-01

The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Analysis of disease-associated objects at the Rat Genome Database

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Wang, Shur-Jen; Laulederkind, Stanley J. F.; Hayman, G. T.; Smith, Jennifer R.; Petri, Victoria; Lowry, Timothy F.; Nigam, Rajni; Dwinell, Melinda R.; Worthey, Elizabeth A.; Munzenmaier, Diane H.; Shimoyama, Mary; Jacob, Howard J.

2013-01-01

The Rat Genome Database (RGD) is the premier resource for genetic, genomic and phenotype data for the laboratory rat, Rattus norvegicus. In addition to organizing biological data from rats, the RGD team focuses on manual curation of gene–disease associations for rat, human and mouse. In this work, we have analyzed disease-associated strains, quantitative trait loci (QTL) and genes from rats. These disease objects form the basis for seven disease portals. Among disease portals, the cardiovascular disease and obesity/metabolic syndrome portals have the highest number of rat strains and QTL. These two portals share 398 rat QTL, and these shared QTL are highly concentrated on rat chromosomes 1 and 2. For disease-associated genes, we performed gene ontology (GO) enrichment analysis across portals using RatMine enrichment widgets. Fifteen GO terms, five from each GO aspect, were selected to profile enrichment patterns of each portal. Of the selected biological process (BP) terms, ‘regulation of programmed cell death’ was the top enriched term across all disease portals except in the obesity/metabolic syndrome portal where ‘lipid metabolic process’ was the most enriched term. ‘Cytosol’ and ‘nucleus’ were common cellular component (CC) annotations for disease genes, but only the cancer portal genes were highly enriched with ‘nucleus’ annotations. Similar enrichment patterns were observed in a parallel analysis using the DAVID functional annotation tool. The relationship between the preselected 15 GO terms and disease terms was examined reciprocally by retrieving rat genes annotated with these preselected terms. The individual GO term–annotated gene list showed enrichment in physiologically related diseases. For example, the ‘regulation of blood pressure’ genes were enriched with cardiovascular disease annotations, and the ‘lipid metabolic process’ genes with obesity annotations. Furthermore, we were able to enhance enrichment of neurological

Monoamines and sexual function in rats bred for increased catatonic reactivity.

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Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

2009-07-01

Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

Aging enhances the vulnerability of mesenchymal stromal cells to uniaxial tensile strain-induced apoptosis.

Science.gov (United States)

McKayed, Katey; Prendergast, Patrick J; Campbell, Veronica A

2016-02-08

Mechanical priming can be employed in tissue engineering strategies to control the fate and differentiation pattern of mesenchymal stromal cells. This is relevant to regenerative medicine whereby mechanical cues can promote the regeneration of a specific tissue type from mesenchymal precursors. The ability of cells to respond to mechanical forces is dependent upon mechanotransduction pathways that involve membrane-associated proteins, such as integrins. During the aging process changes in the mechanotransduction machinery may influence how cells from aged individuals respond to mechanical priming. In this study mesenchymal stromal cells were prepared from young adult and aged rats and exposed to uniaxial tensile strain at 5% and 10% for 3 days, or 2.5% for 7 days. Application of 5% tensile strain had no impact on cell viability. In contrast, application of 10% tensile strain evoked apoptosis and the strain-induced apoptosis was significantly higher in the mesenchymal stromal cells prepared from the aged rats. In parallel to the age-related difference in cellular responsiveness to strain, an age-related decrease in expression of α2 integrin and actin, and enhanced lipid peroxidation was observed. This study demonstrates that mesenchymal stem cells from aged animals have an altered membrane environment, are more vulnerable to the pro-apoptotic effects of 10% tensile strain and less responsive to the pro-osteogenic effects of 2.5% tensile strain. Thus, it is essential to consider how aged cells respond to mechanical stimuli in order to identify optimal mechanical priming strategies that minimise cell loss, particularly if this approach is to be applied to an aged population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biokinetics of radiotellurium in rats

International Nuclear Information System (INIS)

Nishimura, Y.; Sahoo, S.K.; Kim, S.; Homma-Takeda, S.; Watanabe, Y.; Inaba, J.

2003-01-01

Radiotellurium is present in the environment primarily due to its release during nuclear reactor accidents. Little is known of tellurium metabolism in juveniles, although the element is relatively abundant and has a number of industrial uses. A biokinetic study of radiotellurium in rats was done using gamma-ray counting. Wistar strain rats were used to determine the uptake of H 2 123 Te m O 3 by the whole-body retention of juvenile rats and the conceptus in relation to its gestational stages, by measurements in the placenta, fetal membranes, fetal fluid, and fetus. The whole-body retention of 123 Te m in juvenile rats was higher than that of adult rats. The relative concentration in the placenta and fetal membranes was higher than in the fetus. No activity was observed in the fetal fluid. These results indicate that the placenta and fetal membranes play significant roles as barriers to the transfer of 123 Te m into the fetus. The ratio, relative concentration in fetus/relative concentration in mother (C F /C M ), was calculated. The C F /C M ratio was dependent on the stage of gestation and ranged from 0.2 to 0.5. A little 123 Te m was transferred to the suckling rats through the mother's milk when the isotope was administered intravenously to the mother. (author)

A review of the incidence and coincidence of uterine and mammary tumors in Wistar and Sprague-Dawley rats based on the RITA database and the role of prolactin.

Science.gov (United States)

Harleman, Johannes H; Hargreaves, Adam; Andersson, Håkan; Kirk, Sarah

2012-08-01

Wistar rats are frequently selected for use in carcinogenicity studies because of their advantageous survival rate, which is more favorable than other strains such as the Sprague-Dawley (SD) strain. Uterine and mammary tumors are relatively common spontaneous neoplasms of both strains. We examined the incidence and coincidence of uterine tumors and mammary tumors in control animals of both strains within the RITA database. There was a strong inverse relationship between these tumor types in Wistar rats (p 10%.

The resting electrocardiogram of t. cruzi-infected rats

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Reinaldo B. Bestetti

1987-08-01

Full Text Available A total of 125 rats were infected with the Colômbia strain of T. cruzi (2000 parasites/g shortly after weaning. Of these, 58 survived the acute phase and were used in the present experiment. Twenty eight similar but not infected rats served as controls. All rats were submitted to the resting ECG When they were 6 months old. Classic and 3 precordial leads were employed in order to record the ECG as completely as possible. Electrocardiographic changes similar to those found in human chronic Chagas' heart disease and not previously described in this model were found in 44% of the T. cruzi-infected rats: left axis deviation (22%, right axis deviation (7%, lengthened and bizarre QRS complex (14% and abnormal J point elevation (3%. On the basis of these results, we believe that the resting ECG constitutes a valuable tool for studying experimental chronic Chagas' heart disease in rats.

Thyroid and pancreatic hormones in lethally irradiated rats

International Nuclear Information System (INIS)

Ahlersova, E.; Ahlers, I.; Praslicka, M.

1985-01-01

The concentrations of thyroxine, triiodothyronine and reverse triiodothyronine, glucagon and insulin in the serum or plasma were determined by radioimmunoassay in male rats of the Wistar strain 1, 6, 24, 48 and 72 hours after irradiation with 14.35 Gy (1500R) of X-rays. The irradiated and sham-irradiated rats were starved till examination. The concentrations of thyroxine and triiodothyronine dropped 6 hours after irradiation as compared with controls, the concentration of thyroxine also dropped after 72 hours. The level of reverse triiodothyronine in irradiated rats increased in the terminal period. The level of insulin dropped 24 hours after irradiation, at 72 hours it was higher than that in controls. The concentration of glucagon in irradiated rats increased in the terminal phase of radiation disease. The results document the diverse reaction of hormones in lethally irradiated rats and contribute to a deeper recognition of metabolic imbalance in the course of radiation disease. (author)

Genetic control of differential acetylation in diabetic rats.

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Pamela J Kaisaki

Full Text Available Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.

Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat

Energy Technology Data Exchange (ETDEWEB)

Fan, F. (Dept. of Pharmacology, Toxicology and Therapeutics, Univ. of Kansas Medical Center, Kansas City, KS (United States)); Rozman, K.K. (Section of Environmental Toxicology, GSF-Inst. fuer Toxikologie, Neuherberg (Germany))

1994-12-01

The aim of this study was to examine the acute toxicity of TCDD in a rat strain other than the Sprague-Dawley (S-D) rat. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 [mu]g/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T[sub 4] (TT[sub 4]) and total T[sub 3] (TT[sub 3]) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), [gamma]-glutamyl transpeptidase ([gamma]-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic [gamma]-GT activity was also dose-dependently reduced. However, unlike in S-D rats, these dose-responses occurred in a higher dose range than the reduction of PEPCK activity which appears to be the explanation for the decreased susceptibility of L-E rats to TCDD. Serum TT[sub 4] levels were significantly decreased at all doses, whereas the serum concentration of TT[sub 3] appeared unaffected. The results of this study suggest that subtle differences in the regulation of intermediary metabolism between these two strains of rats are responsible for strain differences in the susceptibility to TCDD. (orig.)

Phenotypic characterization of the Komeda miniature rat Ishikawa, an animal model of dwarfism caused by a mutation in Prkg2.

Science.gov (United States)

Tsuchida, Atsuko; Yokoi, Norihide; Namae, Misako; Fuse, Masanori; Masuyama, Taku; Sasaki, Masashi; Kawazu, Shoji; Komeda, Kajuro

2008-12-01

The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BNxKMI-mri/mri)F1xKMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII.

Fenbendazole treatment and litter size in rats.

Science.gov (United States)

Johnston, Nancy A; Bieszczak, Jeremiah R; Verhulst, Steven; Disney, Kimberly E; Montgomery, Kyle E; Toth, Linda A

2006-11-01

Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.

A sucrose-rich diet induces mutations in the rat colon

DEFF Research Database (Denmark)

Dragsted, Lars O.; Daneshvar, Bahram; Vogel, Ulla

2002-01-01

A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we have...... added sucrose to the diet of Big Blue rats, a strain of Fischer rats carrying 40 copies of the lambda-phage on chromosome 4. Dietary sucrose was provided to the rats for 3 weeks at four dose levels including the background level in the purified diet [3.4% (control), 6.9%, 13.8%, or 34.5%] without...... of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes...

Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.

Science.gov (United States)

Xu, Haiyang; Das, Sasmita; Sturgill, Marc; Hodgkinson, Colin; Yuan, Qiaoping; Goldman, David; Grasing, Kenneth

2017-08-01

The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding. The objective of the present study is to compare cocaine preference, neurotransmitter release, and dopamine receptor activation in LS and HS rats. Levels of dopamine, acetylcholine, and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats. HS rats displayed greater conditioned-place preference scores compared to LS and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased locomotor activity in LS rats, but not in HS animals, while high-dose cocaine augmented activity only in HS rats. Either dose of cocaine increased immunoreactivity for c-Fos in the NA shell of both strains, with greater elevations observed in HS rats. Activation identified by cells expressing both c-Fos and dopamine receptors was generally greater in the HS strain, with a similar pattern for both D1 and D2 dopamine receptors. Diminished levels of dopamine and acetylcholine in the NA shell, with enhanced cocaine-induced expression of D1 and D2 receptors, are associated with greater rewarding effects of cocaine in HS rats and an altered dose-effect relationship for cocaine-induced locomotor activity.

Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats

DEFF Research Database (Denmark)

Markussen, Mette Drude Kjær; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

Background: Anticoagulant resistance in Norway rats, Rattus norvegicus (Berk.), has been suggested to be conferred by mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides. Other factors, e.g. pharmacokinetics, may also contribute to resistance, however. To examine......, Cyp3a2 and Cyp3a3 genes. On exposure to bromadiolone, females had higher Cyp2e1 expression than males, which possibly explains why female rats are generally more tolerant to anticoagulants than male rats. Conclusion: results suggest that bromadiolone resistance in a Danish strain of Norway rats...

The Effects of Methylphenidate on Goal-Directed Behavior in a Rat Model of ADHD

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Joman Y. Natsheh

2015-11-01

Full Text Available Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR (ADHD rat model and Wistar-Kyoto rats (WKY, the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate, a commonly used ADHD medication, on goal-directed behavior, we injected rats with either Methylphenidate or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, methylphenidate administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how methylphenidate acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

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Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

2011-06-01

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Lactobacillus salivarius REN counteracted unfavorable 4-nitroquinoline-1-oxide-induced changes in colonic microflora of rats.

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Zhang, Ming; Qiao, Xuewei; Zhao, Liang; Jiang, Lu; Ren, Fazheng

2011-12-01

Probiotics and carcinogens both have a significant effect on the microfloral composition of the human intestine. The objective of this study was to investigate the impact of an important carcinogen, 4-Nitroquinoline-1-Oxide on colonic microflora and the efficacy of the probiotic Lactobacillus salivarius REN as an agent of counteracting these effects. Using denaturing gradient gel electrophoresis (DGGE) combined with redundancy analysis, we demonstrated that both 4-Nitroquinoline-1-Oxide and L. salivarius REN significantly altered the bacterial communities of rat colons. A total of 27 bacterial strains were identified as being affected by treatment with 4-Nitroquinoline-1-Oxide or L. salivarius REN using a t-value biplot combined with band sequencing. 4-Nitroquinoline-1-Oxide treatment increased the abundance of two potential pathogens (one Helicobacter strain and one Desulfovibrio strain), as well as reducing the abundance of two potentially beneficial strains (one Ruminococcaceae strain and one Rumen bacteria). The Helicobacter strain was initally detected in carcinogen-treated rat intestinal microflora, but L. salivarius REN treatment effectively suppressed the growth of the Helicobacter strain. These results suggested that L. salivarius REN may be a potential probiotic, efficiently acting against the initial infection with, and the growth of pathogenic bacteria.

Detection of uncommon G3P[3] rotavirus A (RVA) strain in rat possessing a human RVA-like VP6 and a novel NSP2 genotype.

Science.gov (United States)

Ianiro, Giovanni; Di Bartolo, Ilaria; De Sabato, Luca; Pampiglione, Guglielmo; Ruggeri, Franco M; Ostanello, Fabio

2017-09-01

Rotavirus is one of the leading causes of acute gastroenteritis in infants and young children. RVAs infect not only humans but also a wide range of mammals including rats, which represent a reservoir of several other zoonotic pathogens. Due to the segmented nature of the RVA genome, animal RVA strains can easily adapt to the human host by reassortment with co-infecting human viruses. This study aims to detect and characterize RVA in the intestinal content of Italian sinantropic rats (Rattus rattus). Out of 40 samples examined following molecular approach, one resulted positive for RVA. The molecular characterization of VP1-4, 6 and 7, and NSP1-5 genes by sequencing revealed the genomic constellation G3-P[3]-I1-R11-C11-M10-A22-N18-T14-E18-H13. This uncommon genomic combination includes: the VP1-4,VP7, the NSP1, 3, 4 and 5 gene segments, closely related to those of RVA from rodents, the N18 novel genotype established for the NSP2 gene segment and the human Wa-like VP6 gene, suggesting interspecies reassortment. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypocholesterolemic Effects of Probiotic Mixture on Diet-Induced Hypercholesterolemic Rats

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Shang-Jin Kim

2017-03-01

Full Text Available Growing evidence has indicated that supplementation with probiotics improves lipid metabolism. We aimed to investigate the beneficial effects of a probiotics mixture (PM of three strains belonging to the species Bifidobacterium (B. longum, B. lactis, and B. breve and two strains belonging to the species Lactobacillus (L. reuteri and L. plantarum on cholesterol-lowering efficacy in hypercholesterolemic rats. A hypercholesterolemic rat model was established by feeding a high-cholesterol diet for eight weeks. To test the effects of PM on hypercholesterolemia, hypercholesterolemic rats were assigned to four groups, which were treated daily with low (1.65 × 109 cfu/kg, medium (5.5 × 109 cfu/kg, or high (1.65 × 1010 cfu/kg doses of probiotic mixture or simvastatin for eight weeks. Significant reductions of serum total cholesterol (TC, triacylglycerol (TG, and low-density lipoprotein (LDL-cholesterol levels, but increases of high-density lipoprotein (HDL-cholesterol were observed after supplementation of PM in hypercholesterolemic rats. In PM-supplemented hypercholesterolemic rats, hepatic tissue contents of TC and TG also significantly decreased. Notably, the histological evaluation of liver tissues demonstrated that PM dramatically decreased lipid accumulation. For their underlying mechanisms, we demonstrated that PM reduced expressions of cholesterol synthesis-related proteins such as sterol regulatory element-binding protein 1 (SREBP1, fatty acid synthase (FAS, and acetyl-CoA carboxylase (ACC in the liver. Taken together, these findings suggest that PM has beneficial effects against hypercholesterolemia. Accordingly, our PM might be utilized as a novel therapeutic agent for the management of hypercholesterolemia.

Moderately Low Magnesium Intake Impairs Growth of Lean Body Mass in Obese-Prone and Obese-Resistant Rats Fed a High-Energy Diet

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Jesse Bertinato

2016-04-01

Full Text Available The physical and biochemical changes resulting from moderately low magnesium (Mg intake are not fully understood. Obesity and associated co-morbidities affect Mg metabolism and may exacerbate Mg deficiency and physiological effects. Male rats selectively bred for diet-induced obesity (OP, obese-prone or resistance (OR, obese-resistant were fed a high-fat, high-energy diet containing moderately low (LMg, 0.116 ± 0.001 g/kg or normal (NMg, 0.516 ± 0.007 g/kg Mg for 13 weeks. The growth, body composition, mineral homeostasis, bone development, and glucose metabolism of the rats were examined. OP and OR rats showed differences (p < 0.05 in many physical and biochemical measures regardless of diet. OP and OR rats fed the LMg diet had decreased body weight, lean body mass, decreased femoral size (width, weight, and volume, and serum Mg and potassium concentrations compared to rats fed the NMg diet. The LMg diet increased serum calcium (Ca concentration in both rat strains with a concomitant decrease in serum parathyroid hormone concentration only in the OR strain. In the femur, Mg concentration was reduced, whereas concentrations of Ca and sodium were increased in both strains fed the LMg diet. Plasma glucose and insulin concentrations in an oral glucose tolerance test were similar in rats fed the LMg or NMg diets. These results show that a moderately low Mg diet impairs the growth of lean body mass and alters femoral geometry and mineral metabolism in OP and OR rats fed a high-energy diet.

[Age-related aspects of male rats sexual behavior with different senescence rates].

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Amstislavskaia, T G; Gladkikh, D V; Belousova, I I; Maslova, L N; Kolosova, N G

2010-01-01

Social and sexual behavior of males Wistar and senescence-accelerated OXYS rats was studied. The experimental model excluding direct interaction between partners showed that the exploratory activity decreased with aging in rats of both strains, but social motivation didn't change. No interstrain differences in intensity of sexual motivation in the presence of an inaccessible receptive female were observed in 4-month rats. The level of sexual motivation of 12-month Wistar rats didn't differ from that of 4-month animals. However, in 12-month OXYS males, sexual motivation was decreased as compared to both 4- and 12-month Wistar rats. The same regularities were found under conditions of direct interaction with a partner. Behavioral changes in 12-month OXYS rats were considered as genetically determinate abnormality at the initial stage of sexual behavior, i.e., sexual motivation. The results suggest the accelerated senescence of the reproductive system of OXYS rats.

[Particularities of adrenergic regulation and the function of cardiovascular system at remote periods after myocardial infarction in rats of different strains].

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Belkina, L M; Usacheva, M A; Popkova, E V; Smirnova, E A; Matsievskiĭ, D D; Sazontova, T G; Anchishkina, N A; Kruglov, S V; Terekhina, O L

2009-01-01

Heart function was studied in the August rats with innate raised sympathetic-adrenal system and in the Wistar rats through the period of 3 month after myocardial infarction. The sizes of the postinfarction scars were similar in the rats under comparison (56-62%) but end-diastolic pressure in Wistar rats and in August rats was 18.7 +/- 2.2 mm Hg and 11.8 +/- 0.7 mm Hg. Under the maximum isometric load induced by the aorta coarctation, the work efficiency of the heart in the August rats was greater than in the Wistar rats. During the postinfarction period, plasma catecholamine (CA) in August rats was higher than in Wistar rats. In the adrenal glands, the CA contents in August rats increased and in Wistar rats decreased. The activity of CA resynthes in the adrenal glands and in the hypothalamus in August rats did not change and in Wistar rats increased. The blood contents of nitrate and nitrite and hemine oxygenase-1 level in the myocardium of August rats were increased in contrast to Wistar rats. the higher viability of the myocardium in August rats with long existing postinfarction cardiasclerosis is to a considerable extent associated with lowered activation of the sympathetic-adrenal system under more expressing activation of NO-system and antioxidant protection.

Cyclophilin B expression in renal proximal tubules of hypertensive rats.

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Kainer, D B; Doris, P A

2000-04-01

Rat cyclophilin-like protein (Cy-LP) is a candidate hypertension gene initially identified by differential hybridization and implicated in renal mechanisms of salt retention and high blood pressure. We report the molecular characterization of rat cyclophilin B (CypB) and demonstrate, through sequence analysis and an allele-specific polymerase chain reaction primer assay, that CypB but not Cy-LP is expressed in rat kidney. CypB is an endoplasmic reticulum-localized prolyl-isomerase that interacts with elongation initiation factor 2-beta, an important regulator of protein translation and a central component of the endoplasmic reticulum stress response to hypoxia or ATP depletion. Active renal transport of sodium is increased in the spontaneously hypertensive rat (SHR), and there is evidence that this coincides with hypoxia and ATP depletion in the renal cortex. In the present studies we have examined expression of CypB in rat proximal tubules, which contributes to the increased renal sodium reabsorption in this model of hypertension. We report that CypB transcript abundance is significantly elevated in proximal convoluted tubules from SHR compared with the control Wistar-Kyoto strain. This upregulation occurs in weanling animals and precedes the development of hypertension, indicating that it is not a simple response to hypertension in SHR. Further, CypB expression is also higher in a proximal tubule cell line derived from SHR compared with a similar line derived from Wistar-Kyoto rats, indicating that this difference is genetically determined. No sequence differences were observed in the CypB cDNA from these 2 strains. These observations suggest that a genetically determined alteration in proximal tubules from SHR occurs that leads to increased expression of CypB. In view of evidence linking CypB to the regulation of elongation initiation factor-2, the upregulation of CypB may result from metabolic stress.

A new polymorphic pepsinogen locus (Pg-2) in the rat (Rattus norvegicus).

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Hamada, S; Yamada, J; Bender, K; Adams, M

1987-07-01

Only two types of pepsinogens, which are products of the Pg-1 locus, are present in rat urine. In gastric mucosa, however, additional pepsinogen isozymes are expressed. We have found a polymorphism for rat gastric mucosa pepsinogen using agarose gel electrophoresis. Some inbred rat strains expressed a pepsinogen band, while others did not. The trait was found to be controlled by a single autosomal locus. We tentatively designated the locus as Pg-2 with two alleles, Pg-2a for the one controlling presence of the band and Pg-2o for the one controlling absence. Linkage analysis using BN and TM strains revealed that Pg-2 was closely linked to Pg-1 (3.7 +/- 1.8 cM), and that it did not belong to LG I (Hbb and p), LG II (Acon-1 and Mup-1), LG IV (Hao-1 and Svp-1), LG V (Es-1 and Es-3), LG VI (Gc and h), LG IX (RT1), LG X (Fh and Pep-3), nor a LG containing Ahd-2 (as yet undetermined).

Esophageal morphometric and biomechanical changes during aging in rats

DEFF Research Database (Denmark)

Zhao, Jingbo; Gregersen, Hans

of the present study is to investigate the esophageal geometry and biomechanical changes during aging in rats. Materials and methods Twenty-four male Wistar rats, aged from 6 to 22 months, were used in the study. The body weight and the wet weight per length of esophageal segment were measured at the termination...... was found among 12, 18 and 22 months groups (p>0.05). The longitudinal stress-strain curves shifted from right to the left during aging (pstiffness has no obvious...... change after 12 months in the circumferential direction. Furthermore, we confirm that the esophagus was stiffer in the longitudinal direction than in the circumferential direction. Conclusions A pronounced morphometric and biomechanical remodeling was occurred in the rat esophagus during aging...

Radiosensitivity and thermoresistance of rat RA-2 rhabdomyosarcoma cells

International Nuclear Information System (INIS)

Fedorova, E.V.; Trusova, V.D.; Vakhtin, Yu.B.

1990-01-01

The data obtained show that clonogenic RA-2T cells are 2-3 times more thermoresistant than clonogenic cells of the original thermosensitive RA-2T strain as estimated by D 0 value upon heating up to 43-45 deg C. After X-irradiation of rat rhabdomyosarcoma, a decrease in the capacity of forming pulmonary colonies is more pronounced in cells of the thermosensitive RA-2 strain cells than in those of the thermoresistant strain RA-2T (D 0 =1.6 Gy and D 0 =2.4 Gy, respectively). In all appearance, within one and the same tumor cell population, the hereditarily thermoresistant cells are more radioresistant than the thermosensitive ones

Context and strain-dependent behavioral response to stress

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Baum Amber E

2008-06-01

Full Text Available Abstract Background This study posed the question whether strain differences in stress-reactivity lead to differential behavioral responses in two different tests of anxiety. Strain differences in anxiety-measures are known, but strain differences in the behavioral responses to acute prior stress are not well characterized. Methods We studied male Fisher 344 (F344 and Wistar Kyoto (WKY rats basally and immediately after one hour restraint stress. To distinguish between the effects of novelty and prior stress, we also investigated behavior after repeated exposure to the test chamber. Two behavioral tests were explored; the elevated plus maze (EPM and the open field (OFT, both of which are thought to measure activity, exploration and anxiety-like behaviors. Additionally, rearing, a voluntary behavior, and grooming, a relatively automatic, stress-responsive stereotyped behavior were measured in both tests. Results Prior exposure to the test environment increased anxiety-related measures regardless of prior stress, reflecting context-dependent learning process in both tests and strains. Activity decreased in response to repeated testing in both tests and both strains, but prior stress decreased activity only in the OFT which was reversed by repeated testing. Prior stress decreased anxiety-related measures in the EPM, only in F344s, while in the OFT, stress led to increased freezing mainly in WKYs. Conclusion Data suggest that differences in stressfulness of these tests predict the behavior of the two strains of animals according to their stress-reactivity and coping style, but that repeated testing can overcome some of these differences.

Carriage of methicillin-resistant Staphylococcus aureus by wild urban Norway rats (Rattus norvegicus.

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Chelsea G Himsworth

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA is an important cause of multi-drug-resistant infections in people, particularly indigent populations. MRSA can be transmitted between people and domestic animals, but the potential for transmission between people and commensal pests, particularly rodents, had not been investigated. The objective of this study was to identify the presence and characterize the ecology of MRSA in rats (Rattus spp. from in an impoverished, inner-city neighborhood. Oropharyngeal swabs were collected from rats trapped in 33 city blocks and one location within the adjacent port. Bacterial culture was performed and MRSA isolates were characterized using a variety of methods, including whole-genome sequencing (WGS. The ecology of MRSA in rats was described using phylogenetic analysis, geospatial analysis, and generalized linear mixed models. MRSA was identified 22 of 637 (3.5% rats tested, although prevalence varied from 0 - 50% among blocks. Isolates belonged to 4 clusters according to WGS, with the largest cluster (n = 10 containing isolates that were genetically indistinguishable from community-acquired USA300 MRSA strains isolated from people within the study area. MRSA strains demonstrated both geographic clustering and dispersion. The odds of an individual rat carrying MRSA increased with increased body fat (OR = 2.53, 95% CI = 1.33-4.82, and in the winter (OR = 5.29, 95% CI = 1.04-26.85 and spring (OR = 5.50, 95% CI = 1.10-27.58 compared to the fall. The results show that urban rats carried the same MRSA lineages occurring in local human and/or animal populations, supporting recent transmission from external sources. MRSA carriage was influenced by season, most likely as a result of temporal variation in rat behavior and rat-human interactions.

Sleep deprivation and spike-wave discharges in epileptic rats

NARCIS (Netherlands)

Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Vossen, J.M.H.; Luijtelaar, E.L.J.M. van

1995-01-01

The effects of sleep deprivation were studied on the occurrence of spike-wave discharges in the electroencephalogram of rats of the epileptic WAG/Rij strain, a model for absence epilepsy. This was done before, during and after a period of 12 hours of near total sleep deprivation. A substantial

Long-term characterization of the diet-induced obese and diet-resistant rat model

DEFF Research Database (Denmark)

Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

2010-01-01

, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization......, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents....

Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine.

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Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

2012-03-15

Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of mortality and morbidity in the premature infant. Premature infants have a delay in intestinal colonization by commensal bacteria and colonization with potentially pathogenic organisms. Lactobacillus reuteri is a probiotic that inhibits enteric infections, modulates the immune system, and may be beneficial to prevent NEC. In previous studies, L. reuteri strains DSM 17938 and ATCC PTA 4659 differentially modulated inflammation in vitro; however, the strains had equivalent anti-inflammatory responses in LPS feeding-induced ileitis in neonatal rats in vivo. The impact of these two strains in the prevention of NEC has not been previously investigated. NEC was induced in newborn rats by orogastric formula feeding and exposure to hypoxia. L. reuteri was added to the formula to prevent NEC. NEC score, Toll-like receptor (TLR)-signaling genes, phospho-IκB activity, and cytokine levels in the intestine were examined. Both strains significantly increased survival rate and decreased the incidence and severity of NEC, with optimal effects from DSM 17938. In response to probiotic, mRNA expression of IL-6, TNF-α, TLR4, and NF-κB was significantly downregulated, while mRNA levels of anti-inflammatory cytokine IL-10 were significantly upregulated. In parallel, L. reuteri treatment led to decrease intestinal protein levels of TLR4 and cytokine levels of TNF-α and IL-1β in newborn rats with NEC. Both strains significantly inhibited not only intestinal LPS-induced phospho-IκB activity in an ex vivo study but also decreased the levels of phospho-IκB in the intestines of NEC rat model. Cow milk formula feeding produced a similar but milder proinflammatory profile in the intestine that was also ameliorated by 17938. Our studies demonstrate that each of the two L. reuteri strains has potential therapeutic value in our NEC model and in enteritis associated with cow milk feeding. These results support the

Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

Energy Technology Data Exchange (ETDEWEB)

Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

2010-10-27

Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

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Johnson Cynthia E

2008-09-01

Full Text Available Abstract Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD, short day length (L8:D16; SD, and long day length (L16:D8; LD. We compared nocturnality (the proportion of activity during night or subjective night, duration of activity (alpha, activity onset and offset, phase angle of entrainment, and free running rhythms (tau of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non

Screening and characterization of lactic acid bacterial strains that produce fermented milk and reduce cholesterol levels

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Xuefang Guan

Full Text Available ABSTRACT Objective To screen for and characterize lactic acid bacteria strains with the ability to produce fermented milk and reduce cholesterol levels. Methods The strains were isolated from traditional fermented milk in China. In vitro and in vivo evaluation of cholesterol-reduction were used to identify and verify strains of interest. Characteristics were analyzed using spectrophotometry and plate counting assays. Results The isolate HLX37 consistently produced fermented milk with strong cholesterol-reducing properties was identified as Lactobacillus plantarum (accession number: KR105940 and was thus selected for further study. The cholesterol reduction by strain HLX37 was 45.84%. The isolates were acid-tolerant at pH 2.5 and bile-tolerant at 0.5% (w/v in simulated gastric juice (pH 2.5 for 2 h and in simulated intestinal fluid (pH 8.0 for 3 h. The auto-aggregation rate increased to 87.74% after 24 h, while the co-aggregation with Escherichia coli DH5 was 27.76%. Strain HLX37 was intrinsically resistant to antibiotics such as penicillin, tobramycin, kanamycin, streptomycin, vancomycin and amikacin. Compared with rats in the model hyperlipidemia group, the total cholesterol content in the serum and the liver as well as the atherogenic index of rats in the viable fermented milk group significantly decreased by 23.33%, 32.37% and 40.23%, respectively. Fewer fat vacuoles and other lesions in liver tissue were present in both the inactivated and viable fermented milk groups compared to the model group. Conclusion These studies indicate that strain HLX37 of L. plantarum demonstrates probiotic potential, potential for use as a candidate for commercial use for promoting health.

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

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Brunner Sabine

2011-10-01

Full Text Available Abstract Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF. Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28% or a high-salt diet (5.5% starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food (ZDF+S+E, hydralazine (25 mg/kg per day (ZDF+S+H, or no treatment (ZDF+S. Rats on normal salt-diet were assigned to eplerenone (ZDF+E or no treatment (ZDF. Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL or high-salt diet (ZL+S serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio and vascular stiffness (strain and stress were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition

SWIMMING ENHANCES BONE MASS ACQUISITION IN GROWING FEMALE RATS

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Joanne McVeigh

2010-12-01

Full Text Available Growing bones are most responsive to mechanical loading. We investigated bone mass acquisition patterns following a swimming or running exercise intervention of equal duration, in growing rats. We compared changes in bone mineral properties in female Sprague Dawley rats that were divided into three groups: sedentary controls (n = 10, runners (n = 8 and swimmers (n = 11. Runners and swimmers underwent a six week intervention, exercising five days per week, 30min per day. Running rats ran on an inclined treadmill at 0.33 m.s-1, while swimming rats swam in 25oC water. Dual energy X-ray absorptiometry scans measuring bone mineral content (BMC, bone mineral density (BMD and bone area at the femur, lumbar spine and whole body were recorded for all rats before and after the six week intervention. Bone and serum calcium and plasma parathyroid hormone (PTH concentrations were measured at the end of the 6 weeks. Swimming rats had greater BMC and bone area changes at the femur and lumbar spine (p < 0.05 than the running rats and a greater whole body BMC and bone area to that of control rats (p < 0.05. There were no differences in bone gain between running and sedentary control rats. There was no significant difference in serum or bone calcium or PTH concentrations between the groups of rats. A swimming intervention is able to produce greater beneficial effects on the rat skeleton than no exercise at all, suggesting that the strains associated with swimming may engender a unique mechanical load on the bone

Strain and sex differences in puberty onset and the effects of THC administration on weight gain and brain volumes.

Science.gov (United States)

Keeley, R J; Trow, J; McDonald, R J

2015-10-01

The use of recreational marijuana is widespread and frequently begins and persists through adolescence. Some research has shown negative consequences of adolescent marijuana use, but this is not seen across studies, and certain factors, like genetic background and sex, may influence the results. It is critical to identify which characteristics predispose an individual to be susceptible to the negative consequences of chronic exposure to marijuana in adolescence on brain health and behavior. To this end, using males and females of two strains of rats, Long-Evans hooded (LER) and Wistar (WR) rats, we explored whether these anatomically and behaviorally dimorphic strains demonstrated differences in puberty onset and strain-specific effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana. Daily 5 mg/kg treatment began on the day of puberty onset and continued for 14 days. Of particular interest were metrics of growth and volumetric estimates of brain areas involved in cognition that contain high densities of cannabinoid receptors, including the hippocampus and its subregions, the amygdala, and the frontal cortex. Brain volumetrics were analyzed immediately following the treatment period. LER and WR females started puberty at different ages, but no strain differences were observed in brain volumes. THC decreased weight gain throughout the treatment period for all groups. Only the hippocampus and some of its subregions were affected by THC, and increased volumes with THC administration was observed exclusively in females, regardless of strain. Long-term treatment of THC did not affect all individuals equally, and females displayed evidence of increased sensitivity to the effects of THC, and by extension, marijuana. Identifying differences in adolescent physiology of WR and LER rats could help determine the cause for strain and sex differences in brain and behavior of adults and help to refine the use of animal models

A glycoprotein with anti-inflammatory properties secreted by an Aspergillus nidulans modified strain

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J. C. F. Queiroz

2007-01-01

Full Text Available Total RNA from lipopolysaccharide (LPS-stimulated rat macrophages used to treat protoplasts from an Aspergillus nidulans strain originated the RT2 regenerated strain, whose culture supernatant showed anti-inflammatory activity in Wistar rats. The protein fraction presenting such anti-inflammatory activity was purified and biochemically identified. The screening of the fraction responsible for such anti-inflammatory property was performed by evaluating the inhibition of carrageenan-induced paw edema in male Swiss mice. Biochemical analyses of the anti-inflammatory protein used chromatography, carbohydrates quantification of the protein sample, amino acids content analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Total sugar quantification revealed 32% glycosylation of the protein fraction. Amino acid analysis of such fraction showed a peculiar pattern presenting 29% valine. SDS-PAGE revealed that the protein sample is pure and its molecular weight is about 40kDa. Intravenous injection of the isolated substance into mice significantly inhibited carrageenan-induced paw edema. The isolated glycoprotein decreased carrageenan-induced paw edema in a prostaglandin-dependent phase, suggesting an inhibitory effect of the isolated glycoprotein on prostaglandin synthesis.

Angiotensin-converting enzyme inhibitory activity of Lactobacillus helveticus strains from traditional fermented dairy foods and antihypertensive effect of fermented milk of strain H9.

Science.gov (United States)

Chen, Yongfu; Liu, Wenjun; Xue, Jiangang; Yang, Jie; Chen, Xia; Shao, Yuyu; Kwok, Lai-yu; Bilige, Menghe; Mang, Lai; Zhang, Heping

2014-11-01

Hypertension is a major global health issue which elevates the risk of a large world population to chronic life-threatening diseases. The inhibition of angiotensin-converting enzyme (ACE) is an effective target to manage essential hypertension. In this study, the fermentation properties (titratable acidity, free amino nitrogen, and fermentation time) and ACE-inhibitory (ACEI) activity of fermented milks produced by 259 Lactobacillus helveticus strains previously isolated from traditional Chinese and Mongolian fermented foods were determined. Among them, 37 strains had an ACEI activity of over 50%. The concentrations of the antihypertensive peptides, Ile-Pro-Pro and Val-Pro-Pro, were further determined by ultra performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. The change of ACEI activity of the fermented milks of 3 strains exhibiting the highest ACEI activity upon gastrointestinal protease treatment was assayed. Fermented milks produced by strain H9 (IMAU60208) had the highest in vitro ACEI activity (86.4 ± 1.5%), relatively short fermentation time (7.5 h), and detectable Val-Pro-Pro (2.409 ± 0.229 µM) and Ile-Pro-Pro (1.612 ± 0.114 µM) concentrations. Compared with the control, a single oral dose of H9-fermented milk significantly attenuated the systolic, diastolic, and mean blood pressure of spontaneously hypertensive rats (SHR) by 15 to 18 mmHg during the 6 to 12 h after treatment. The long-term daily H9-fermented milk intake over 7 wk exerted significant antihypertensive effect to SHR, but not normotensive rats, and the systolic and diastolic blood pressure were significantly lower, by 12 and 10 mmHg, respectively, compared with the control receiving saline. The feeding of H9-fermented milk to SHR resulted in a significantly higher weight gain at wk 7 compared with groups receiving saline, commercial yogurt, and captopril. Our study identified a novel probiotic L. helveticus strain originated from kurut sampled from Tibet

DETERMINATION OF THE SPECTRUM OF ANTIBIOTIC RESISTANCE GENES HAVE PHENOTYPIC RESISTANT STRAINS OF PARIETAL INTESTINAL MICROBIOTA IN RATS BY RT-PCR

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Bukina Y.V.

2016-06-01

Full Text Available Introduction. The problem of formation of bacterial resistance to glycopeptides and beta-lactam antibiotics (cephalosporins and carbapenems are used worldwide for the treatment of severe community acquired and nosocomial infections, especially caused by polymicrobial flora has become global and is a major factor limiting the effectiveness of antibiotic therapy. In this regard, the study of genetic microbial resistance determinants allows not only to carry out an effective antibiotic therapy, but also to identify two main processes leading to the development of epidemiologically significant events: the introduction of the agent in the risk population from the outside and in situ pathogen (spontaneous genetic drift targeted restructuring of the population. Therefore, the aim of our study was to investigate the resistance genes to carbapenems, cephalosporins, glycopeptides have clinically important phenotype of resistant strains of microorganisms families Enterobacteriaceae, Pseudomonadaceae, Bacteroidaceae, Enterococcaceae, Peptostreptococcaceae. Materials and methods. As a material for PCR studies 712 phenotypically resistant strains of microorganisms isolated from 80 rats "Wistar" line in microbiological study microflora of the wall were used. During the investigation 474 isolates of bacteria of the family Enterobacteriaceae, 39 - Pseudomonadaceae, 71 - Bacteroidaceae, 96 - Enterococcaceae, 32 - Peptostreptococcaceae were studied. Isolation of DNA from bacteria in the study was performed using reagents "DNA-Express" ("Litekh", Russia. For the detection of resistance genes by PCR in real time (RT-PCR reagent kits "FLUOROPOL-RV" ("Litekh", Russia were used. During the experiment, the VIM genes, OXA-48, NDM, KPC, responsible for the resistance of microorganisms to carbapenems, CTX-M - resistance to cephalosporins, as well as genes Van A and van B, the development of resistance to glycopeptides (vancomycin and teicoplanin were determined. Analysis

The increased concentration of 2,3-diphosphoglycerate in red blood cells of spontaneously hypertensive rats.

Science.gov (United States)

Przybylski, J; Skotnicka-Fedorowicz, B; Lisiecka, A; Siński, M; Abramczyk, P

1997-12-01

It has been recognised that high haemoglobin oxygen capacity is essential for the development of high blood pressure in spontaneously hypertensive rats. In the present study we have found increased concentration of 2,3 diphosphoglycerate (2,3-DPG) in red blood cells of spontaneously hypertensive rats (SHR) of Okamoto-Aoki strain. As 2,3-DPG is the major factor decreasing haemoglobin affinity to oxygen, our finding suggests that at given value of pO2 oxygen delivery to the tissue of SHR would be increased. Therefore increased concentration of 2,3-DPG in red blood cells of SHR would be of the pathophysiological meaning by promoting autoregulatory increase in total vascular resistance in this strain of rats. The mechanism responsible for enhanced synthesis of 2,3-DPG in SHR remains unclear. Intracellular alkalosis due to either hypocapnia and/or an enhanced activity of Na+/H+ antiporter occurring in SHR are the most plausible explanations for the above finding.

Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

1988-01-01

Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

Hepatic transcriptomic responses to TCDD in dioxin-sensitive and dioxin-resistant rats during the onset of toxicity

International Nuclear Information System (INIS)

Boutros, Paul C.; Yao, Cindy Q.; Watson, John D.; Wu, Alexander H.; Moffat, Ivy D.; Prokopec, Stephenie D.; Smith, Ashley B.; Okey, Allan B.; Pohjanvirta, Raimo

2011-01-01

The dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a wide range of toxic effects in rodent species, all of which are mediated by a ligand-dependent transcription-factor, the aryl hydrocarbon receptor (AHR). The Han/Wistar (Kuopio) (H/W) strain shows exceptional resistance to many TCDD-induced toxicities; the LD 50 of > 9600 μg/kg for H/W rats is higher than for any other wild-type mammal known. We previously showed that this resistance primarily results from H/W rats expressing a variant AHR isoform that has a substantial portion of the AHR transactivation domain deleted. Despite this large deletion, H/W rats are not entirely refractory to the effects of TCDD; the variant AHR in these animals remains fully competent to up-regulate well-known dioxin-inducible genes. TCDD-sensitive (Long-Evans, L-E) and resistant (H/W) rats were treated with either corn-oil (with or without feed-restriction) or 100 μg/kg TCDD for either four or ten days. Hepatic transcriptional profiling was done using microarrays, and was validated by RT-PCR analysis of 41 genes. A core set of genes was altered in both strains at all time points tested, including CYP1A1, CYP1A2, CYP1B1, Nqo1, Aldh3a1, Tiparp, Exoc3, and Inmt. Outside this core, the strains differed significantly in the breadth of response: three-fold more genes were altered in L-E than H/W rats. At ten days almost all expressed genes were dysregulated in L-E rats, likely reflecting emerging toxic responses. Far fewer genes were affected by feed-restriction, suggesting that only a minority of the TCDD-induced changes are secondary to the wasting syndrome.

Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.

Science.gov (United States)

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Liu, Yunlong; Edenberg, Howard J; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-10-08

Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans and animal models identified chromosomal regions linked to hip size and bone mass. Previously, we identified that the region of 4q21-q41 on rat chromosome (Chr) 4 harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. The purpose of this study is to identify the candidate genes for femoral neck structure and density by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. RNA was extracted from proximal femora of 4-wk-old rats from F344 and LEW strains, and two other strains, Copenhagen 2331 and Dark Agouti, were used as a negative control. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 arrays. A total of 99 genes in the 4q21-q41 region were differentially expressed (P level of the gene in that strain. A total of 18 candidate genes were strongly correlated (r(2) > 0.50) with femoral neck width and prioritized for further analysis. Quantitative PCR analysis confirmed 14 of 18 of the candidate genes. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to angiogenesis (VEGF), bone growth (FGF2), bone formation (IGF2 and IGF2BP3), and resorption (TNF). This study provides a shortened list of genetic determinants of skeletal traits at the hip and may lead to novel approaches for prevention and treatment of hip fracture.

Modification of the β-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.

Science.gov (United States)

Jiang, Cheng; Carillion, Aude; Na, Na; De Jong, Audrey; Feldman, Sarah; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Amour, Julien

2015-07-01

Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates β-adrenoceptors, the β-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the β-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats. Experimental, prospective study. University medical research laboratory. Adult male Zucker lean (control), obese, and obese diabetic rats. The effects of β-adrenoceptor stimulation were investigated in vitro in isolated left ventricular papillary muscles in control, obese, and obese diabetic rats. β1-, β2-, and β3-adrenoceptors and multidrug resistance-associated protein 4 were quantified by Western Blotting. Triglyceride, cholesterol, leptin, adiponectin, and C-peptide plasma concentrations were measured. Data are mean ± SD. Hyperlipidemia, high leptin, and C-peptide concentrations were observed in obese and obese diabetic strains, whereas hyperglycemia occurred only in the diabetic strain. The positive inotropic effect of isoproterenol was slightly reduced in obese rats (183% ± 11% of baseline; p = 0.003; n = 7) and markedly reduced in obese diabetic rats (137% ± 18% of baseline; p < 0.001; n = 10) when compared with control rats (210% ± 17% of baseline; n = 9). β1-adrenoceptors were down-regulated in obese (-41%; p = 0.02) and diabetic (-54%; p = 0.003) when compared with control rats, whereas β3-adrenoceptors and multidrug resistance-associated protein expression remained unchanged. Direct stimulation of adenylate cyclase with forskolin or administration of 3',5'-cyclic adenosine monophosphate suggests that subtle impairments also occurred beside the down-regulation of β1-adrenoceptor. The positive inotropic effect of β-adrenoceptor stimulation is slightly decreased in Zucker obese rats and was more markedly decreased in Zucker diabetic rats. These decreases are mainly related to β1-adrenoceptor down-regulation.

Two new nontoxic, non-pathogenic strains of Sphingomonas elodea for gellan gum production.

Science.gov (United States)

Dolan, Laurie C; Matulka, Ray A; LeBeau, Alex L; Boulet, Jamie M

2016-07-01

Two new strains of Sphingomonas elodea (designated as PHP1 and PBAD1) were tested for toxicity and pathogenicity in healthy Sprague-Dawley CD(®) IGS rats in separate studies. In each study, twelve rats/sex were administered ≥10(8) viable cells/rat by oral gavage, and four untreated rats/sex served as controls. Blood, feces, and selected organs/tissues collected at various times over the course of the 22 day study were evaluated for the presence of PHP1 or PBAD1 (depending on the study) by a validated method, to determine the potential for survival, propagation, or infectivity of PHP1 and PBAD1 cells in the rat. No mortalities, test substance-related changes in clinical or macroscopic findings, body weight or body weight gain were observed in treated animals compared with controls, indicating a lack of toxicity. PHP1 or PBAD1 were not detected in the tissue, fecal or fluid samples collected from treated animals. Therefore, neither PHP1 nor PBAD1 were pathogenic or acutely toxic under the conditions of the studies. Copyright © 2016. Published by Elsevier Inc.

Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats

Energy Technology Data Exchange (ETDEWEB)

Franc, Monique A. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Johnson and Johnson Pharmaceutical Research and Development, Department of Pharmacogenomics, 1000 Route 202 South, P.O. Box 300, Raritan, NJ (United States); Moffat, Ivy D.; Boutros, Paul C.; Okey, Allan B. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Tuomisto, Jouni T.; Tuomisto, Jouko [National Public Health Institute, Department of Environmental Health, Centre for Environmental Health Risk Analysis, Kuopio (Finland); Pohjanvirta, Raimo [University of Helsinki, Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, Helsinki (Finland)

2008-11-15

Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a ''Type-I'' response - that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response - defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 {mu}g/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were

[Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion].

Science.gov (United States)

Sazontova, T G; Belkina, L M; Zhukova, A G; Kirillina, T N; Arkhipenko, Iu V

2004-01-01

In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion. It may thus be concluded that the higher stability of antiradical protection parameters in August rats is one of the mechanisms responsible for the enhanced resistance of the heart to ischemia- and reperfusion-induced injuries.

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

Science.gov (United States)

Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Matsushita, Kohei; Nishikawa, Akiyoshi; Imaida, Katsumi; Ogawa, Kumiko

2017-01-01

3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD in Han/Wistar and Long–Evans rats with different aryl hydrocarbon receptor (AhR structures

Directory of Open Access Journals (Sweden)

Sabrina B. Sholts

2015-01-01

Full Text Available Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W and dioxin-sensitive Long–Evans (L–E rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM and dose–response modeling. The strongest effects were shown by L–E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs for cranial size reduction in L–E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L–E rats, respectively, most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L–E rats had vaults and bases of comparable size, the face was 6.4% larger in L–E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on

TCDD-induced transcriptional profiles in different mouse strains that have an identical AhR genotype

Energy Technology Data Exchange (ETDEWEB)

Wu, Qing; Suzuki, Junko S.; Tohyama, Chiharu; Ohsako, Seiichiroh [Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba (Japan); Takei, Teiji [Environmental Health and Safety Division, Ministry of the Environment, Kasumigaseki, Tokyo (Japan); Lin, Tinmin; Peterson, R.E. [Wisconsin Univ., Wisconsin, MA (United States). School of Pharmacy and Molecular and Environmental Toxicology Center

2004-09-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that is known to cause hepatotoxicity, teratogenicity and carcinogenicity. A characteristic feature in the toxicity of TCDD is exceptionally large differences in susceptibility among animal species or even strains belonging to the same species. These strain differences in susceptibility to TCDD have now been elucidated to be due to the difference in ligand binding affinity or transcriptional activity of the aryl hydrocarbon receptor (AhR). Actually the C57BL/6 type AhR (AhR{sup b}) showed 6-fold higher ligand binding affinity than the DBA/2 type AhR (AhR{sup d}). The H/W rat AhR has a C-terminal truncation of the transactivating domain compared to the L-E rat AhR. On the other hand, there is considerable species variability in response sensitivity to TCDD that cannot be ascribed simply to polymorphisms of the AhR gene. A non-AhR gene susceptibility loci for hepatic porphyria has been observed in mice treated with iron compounds prior to TCDD injection by using a quantitative trait locus analysis of an F2 intercross between susceptible C57BL/6 and resistant DBA/2 stains. In the rat, a gene B with Han/Wistar type AhR is likely to be involved in resistance to TCDD lethality. These observations suggest that other modulating genes, so-called ''modifier genes'', have profound effects on the AhR-mediated gene expression phenotype. Based on the nucleotide sequence of the AhR coding region, the BALB/c, CBA/J, and C3H/He mouse strains are clustered together on a single branch. In the present study, we try to confirm the existence of modifiers by using microarray analysis to examine hepatic gene expression after TCDD exposure in BALB/c, CBA/J, and C3H/He mice. To recognize the existence of a modifier besides the AhR, it is a prerequisite experimental condition that the analyzed strains have an identical AhR genotype. Therefore, we selected BALB/c, CBA/J, and C3H/He mice as the model

Individual variation in aggression of feral rodent strains : A standard for the genetics of aggression and violence?

NARCIS (Netherlands)

de Boer, S.F.; van der Vegt, B.J.; Koolhaas, J.M.

This article summarizes the broad individual differences in aggressiveness and its relationship with several other behavioral, physiological, and neurobiological characteristics that exist in an outbred laboratory strain of male feral rats. Based on the observations that the individual level of

Whole-body γ-irradiation decelerates rat hepatocyte polyploidization.

Science.gov (United States)

Ikhtiar, Adnan M

2015-07-01

To characterize hepatocyte polyploidization induced by intermediate dose of γ-ray. Male Wistar strain rats were whole-body irradiated (WBI) with 2 Gy of γ-ray at the age of 1 month, and 5-6 rats were sacrificed monthly at 0-25 months after irradiation. The nuclear DNA content of individual hepatocytes was measured by flow cytometry, then hepatocytes were classified into various ploidy classes. Survival percentage, after exposure up to the end of the study, did not indicate any differences between the irradiated groups and controls. The degree of polyploidization in hepatocytes of irradiated rats, was significantly lower than that for the control after 1 month of exposure, and it continued to be lower after up to 8 months. Thereafter, the degree of polyploidization in the irradiated group slowly returned to the control level when the irradiated rats reached the age of 10 months. Intermediate dose of ionizing radiation, in contrast to high doses, decelerate hepatocyte polyploidization, which may coincides with the hypothesis of the beneficial effects of low doses of ionizing radiation.

Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

International Nuclear Information System (INIS)

Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

1991-01-01

Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

Quantitative analysis of rat Ig (sub)classes binding to cell surface antigens

International Nuclear Information System (INIS)

Nilsson, R.; Brodin, T.; Sjoegren, H.-O.

1982-01-01

An indirect 125 I-labeled protein A assay for detection of cell surface-bound rat immunoglobulins is presented. The assay is quantitative and rapid and detects as little as 1 ng of cell surface-bound Ig. It discriminates between antibodies belonging to different IgG subclasses, IgM and IgA. The authors describe the production and specificity control of the reagents used and show that the test can be used for quantitative analysis. A large number of sera from untreated rats are tested to evaluate the frequency of falsely positive responses and variation due to age, sex and strain of rat. With this test it is relatively easy to quantitate the binding of classes and subclasses of rat immunoglobulins in a small volume (6 μl) of untreated serum. (Auth.)

The ovarian cycle in rats: a long term EEG study

NARCIS (Netherlands)

Luijtelaar, E.L.J.M. van; Budziszewska, B.; Jaworska-Feil, L.; Ellis, J.L.; Coenen, A.M.L.; Lason, W.; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.; Luijtelaar, E.L.J.M. van

2000-01-01

Rats of the WAG/Rij strain are considered as a genetic model for generalised absence epilepsy. The relationship between the phase of the estrous cycle and the number of spontaneously occurring spike-wave discharges (SWDs) was investigated during the 4 days of the cycle. Vaginal smears were daily

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

Science.gov (United States)

Wolf, Peter

2017-06-01

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of treatment with melatonin on cerebral circulation in old rats

Science.gov (United States)

Dupuis, François; Régrigny, Olivier; Atkinson, Jeffrey; Limiñana, Patrick; Delagrange, Philippe; Scalbert, Elizabeth; Chillon, Jean-Marc

2004-01-01

Melatonin deprival in young rats induces alterations in cerebral arteriolar wall similar to those observed during aging: atrophy and a decrease in distensibility. In this study, we examined the effects of melatonin treatment on cerebral arteriolar structure and distensibility and on the lower limit of cerebral blood flow autoregulation (LLCBF) in old rats. We measured cerebral blood flow (arbitrary unit, laser Doppler, open skull preparation) prior to and during stepwise hypotension (SH) in adult (12/13 months) and old (24/25 months) IcoWI and WAG/Rij male rats. Old rats were untreated or treated for 3 months with melatonin (0.39 (IcoWi) and 0.44 (Wag/Rij) mg kg−1 day−1, drinking water). Stress–strain relationships were determined using cross-sectional area (CSA, μm2, histometry) and values of arteriolar internal diameter (μm) obtained during a second SH following arteriolar deactivation (EDTA, 67 mmol l−1). Aging induced (a) atrophy of the arteriolar wall in IcoWI (616±20 vs 500±27 μm2, P<0.05) but not in WAG/Rij rats (328±25 vs 341±20 μm2), (b) a decrease in arteriolar wall distensibility and (c) an increase in the LLCBF in both strains (67±10 mmHg in 12-month-old vs 95±6 mmHg in 24-month-old IcoWi, P<0.05 and 53±2 mmHg in 13-month-old vs 67±6 mmHg in 25-month-old WAG/Rij). Melatonin treatment induced in IcoWI and WAG/Rij rats (a) hypertrophy of the arteriolar wall (643±34 and 435±25 μm2, respectively), (b) an increase in arteriolar wall distensibility and (c) a decrease in the LLCBF (64±6 and 45±4 mmHg, respectively). Melatonin treatment of old rats induced hypertrophy of the arteriolar wall, prevented the age-linked decrease in cerebral arteriolar distensibility and decreased the LLCBF. PMID:14718260

Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics

NARCIS (Netherlands)

Smits, B.M.; Peters, T.A.; Mul, J.D.; Croes, H.J.; Fransen, J.A.; Beynon, A.J.; Guryev, V.; Plasterk, R.; Cuppen, E.

2005-01-01

The rat is the most extensively studied model organism and is broadly used in biomedical research. Current rat disease models are selected from existing strains and their number is thereby limited by the degree of naturally occurring variation or spontaneous mutations. We have used ENU mutagenesis

Lactococcus lactis is capable of improving the riboflavin status in deficient rats

OpenAIRE

LeBlanc, Jean Guy; Burgess, Catherine M.; Sesma, Fernando; de Giori, Graciela Savoy; van Sinderen, Douwe

2005-01-01

Lactococcus lactis is a commonly used starter strain that can be converted from a vitamin B2 consumer into a vitamin B2 'factory' by over-expressing its riboflavin biosynthesis genes. The present study was conducted to assess in a rat bioassay the response of riboflavin produced by GM or native lactic acid bacteria (LAB). The riboflavin-producing strains were able to eliminate most physiological manifestations of ariboflavinosis such as stunted growth, elevated erythrocyte glutathione reducta...

Validation of Shape Context Based Image Registration Method Using Digital Image Correlation Measurement on a Rat Stomach

DEFF Research Database (Denmark)

Liao, Donghua; Wang, P; Zhao, Jingbo

2014-01-01

Recently we developed analysis for 3D visceral organ deformation by combining the shape context (SC) method with a full-field strain (strain distribution on a whole 3D surface) analysis for calculating distension-induced rat stomach deformation. The surface deformation detected by the SC method...... needs to be further verified by using a feature tracking measurement. Hence, the aim of this study was to verify the SC method-based calculation by using digital image correlation (DIC) measurement on a rat stomach. The rat stomach exposed to distension pressures 0.0, 0.2, 0.4, and 0.6 kPa were studied...... and the SC calculated correspondence surface was compared. Compared with DIC measurement, the SC calculated surface had errors from 5% to 23% at pressures from 0.2 to 0.6 kPa with different surface sample counts between the reference surface and the target surface. This indicates good qualitative...

TCDD dysregulation of 13 AHR-target genes in rat liver

International Nuclear Information System (INIS)

Watson, John D.; Prokopec, Stephenie D.; Smith, Ashley B.; Okey, Allan B.; Pohjanvirta, Raimo; Boutros, Paul C.

2014-01-01

Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 μg/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED 50 equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules following

TCDD dysregulation of 13 AHR-target genes in rat liver

Energy Technology Data Exchange (ETDEWEB)

Watson, John D., E-mail: john.watson@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Prokopec, Stephenie D., E-mail: stephenie.prokopec@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Smith, Ashley B., E-mail: ashleyblaines@gmail.com [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Okey, Allan B., E-mail: allan.okey@utoronto.ca [Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: paul.boutros@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

2014-02-01

Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 μg/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED{sub 50} equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules

Screening and characterization of lactic acid bacterial strains that produce fermented milk and reduce cholesterol levels.

Science.gov (United States)

Guan, Xuefang; Xu, Qingxian; Zheng, Yi; Qian, Lei; Lin, Bin

To screen for and characterize lactic acid bacteria strains with the ability to produce fermented milk and reduce cholesterol levels. The strains were isolated from traditional fermented milk in China. In vitro and in vivo evaluation of cholesterol-reduction were used to identify and verify strains of interest. Characteristics were analyzed using spectrophotometry and plate counting assays. The isolate HLX37 consistently produced fermented milk with strong cholesterol-reducing properties was identified as Lactobacillus plantarum (accession number: KR105940) and was thus selected for further study. The cholesterol reduction by strain HLX37 was 45.84%. The isolates were acid-tolerant at pH 2.5 and bile-tolerant at 0.5% (w/v) in simulated gastric juice (pH 2.5) for 2h and in simulated intestinal fluid (pH 8.0) for 3h. The auto-aggregation rate increased to 87.74% after 24h, while the co-aggregation with Escherichia coli DH5 was 27.76%. Strain HLX37 was intrinsically resistant to antibiotics such as penicillin, tobramycin, kanamycin, streptomycin, vancomycin and amikacin. Compared with rats in the model hyperlipidemia group, the total cholesterol content in the serum and the liver as well as the atherogenic index of rats in the viable fermented milk group significantly decreased by 23.33%, 32.37% and 40.23%, respectively. Fewer fat vacuoles and other lesions in liver tissue were present in both the inactivated and viable fermented milk groups compared to the model group. These studies indicate that strain HLX37 of L. plantarum demonstrates probiotic potential, potential for use as a candidate for commercial use for promoting health. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

Science.gov (United States)

2016-01-01

ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

Science.gov (United States)

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Evidence should trump intuition by preferring inbred strains to outbred stocks in preclinical research.

Science.gov (United States)

Festing, Michael F W

2014-01-01

Inbred strains of mice such as C57BL and BALB/c are more widely used in published work than outbred stocks of mice such as ICR and CD-1. In contrast, outbred stocks of rats such as Wistar and Sprague-Dawley are more widely used than inbred strains such as F344 and LEW. The properties of inbred and outbred mice and rats are briefly reviewed, and it is concluded that, with some exceptions, there is a strong case for using inbred strains in most controlled experiments. This is because they are usually more uniform, so that fewer animals are usually needed to detect a specified response and they are more repeatable, because they are genetically defined (i.e., the strain can be identified using genetic markers) and less liable to genetic change. Yet many scientists continue to use outbred animals. In Daniel Kahneman's book "Thinking Fast and Slow" he explains that we can answer questions in 2 ways: "fast" by intuition or "slow" by analytical reasoning. The former method is instantaneous, requires no thought but is not evidence based. Analytical reasoning is evidence based but requires hard work, which we all avoid. He has found that "… when faced with a difficult question, we often answer an easier one instead, usually without noticing the substitution." The target question of whether to choose outbred or inbred strains in controlled experiments is a difficult one requiring knowledge of the characteristics of these strains and the principles of experimental design. A substitute question, "are humans and outbred stocks both genetically heterogeneous," is easily answered in the affirmative. It is likely that many scientists are intuitively answering the substitute question and are assuming that they have answered the target question. If so they may be using the wrong animals in their research. Nor is the fact that humans and outbred stocks are alike in being genetically heterogeneous a reason for using them. The whole concept of a "model" is that it is similar to the

Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

Science.gov (United States)

Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

2013-05-01

Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line

OpenAIRE

Israel, Yedy; Karahanian, Eduardo; Ezquer, Fernando; Morales, Paola; Ezquer, Marcelo; Rivera-Meza, Mario; Herrera-Marschitz, Mario; Quintanilla, María E.

2017-01-01

This review article addresses the biological factors that influence: (i) the acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake; and (iii) alcohol relapse-like drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%?95%) for rats to display ethanol?s reinforcing effects and to initiate chronic ethanol in...

Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder.

Science.gov (United States)

Pandolfo, Pablo; Vendruscolo, Leandro F; Sordi, Regina; Takahashi, Reinaldo N

2009-08-01

Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking. To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a "normal" genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB(1) cannabinoid receptor and (2) on putative changes by WIN in blood pressure. WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats. In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB(1)-mediated and not related to blood pressure. The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.

Biomechanical and morphological remodelings of gastrointestinal tract in STZ-induced diabetic rats

DEFF Research Database (Denmark)

Sha, Hong; Zhao, Jingbo; Liu, Gui-Fang

2012-01-01

AIM: The aim of the study was to investigate the biomechanical and morphometrical remodeling of gastrointestinal (GI) tract in streptozotocin (STZ) induced diabetic rats. METERIALS AND METHODS： Eighteen SD male rats of diabetic group（DM, a single tail vein injection 40mg／kg of STZ, 9 rats...... in the esophageal, jejunal and colonic segments. RESULTS: The blood glucose level, the wet weight per unit to body weight ratio, wall thickness, opening angle, absolute value of residual strain in DM group were significantly higher than those in C0N group (Pstiffness of the esophageal......, jejunal, colonic wall in circumferential direction and the esophageal, colonic wall in longitudinal direction increased in DM group compared those with CON group (P

Serum glucose and liver glycogen in gamma irradiated rats

International Nuclear Information System (INIS)

Ahlersova, E.; Ahlers, I.; Molcanova, A.

1988-01-01

Overnight fasted male rats of Wistar strain were irradiated with single whole-body doses of 4.78-7.17-9.57 and 14.35 Gy of gamma rays. After decapitation at intervals 1-28 d (4.78 and 7.17 Gy), 1-7 d (9.57 Gy) and 1-3 d (14.35 Gy) glucose concentration in serum and glycogen concentration in liver of irradiated and non-irradiated animals were determined. The higher was radiation dose the more expressive extent and depth of changes (hyperglycemia, accumulation of glycogen) occured. Blood glucose and liver glycogen may serve as a reliable and dose-dependent biological indicators of metabolic changes in irradiated rats. (author)

Effect of passive smoking on the levels of pregnancy associated plasma protein-A in normal rats

International Nuclear Information System (INIS)

Naveed, A.K.; Rahim, A.; Malik, M.S.

2010-01-01

To measure the levels of pregnancy associated plasma protein- A (PAPPA-A) in normal rats exposed to cigarette smoke. Sixty albino rats of Sprague- Dawley strain weighing 200-250 gm, divided into two groups. Both the groups were kept in identical chambers. One group of 30 rats was further exposed to passive cigarette smoke for 4 weeks. No increase was observed in the levels of serum PAPP-A of both the groups: Passive smokers and not exposed to passive smoking i.e. P > 0.05. Smoking does not increase the levels of PAPP-A. (author)

Vitamin K deficiency in SPF-rats fed a semisynthetic irradiated diet

Energy Technology Data Exchange (ETDEWEB)

Juhr, N C; Dietzel, L; Horn, J [Freie Universitaet, Berlin(West). Fachbereich Veterinaermedizin

1975-01-01

A case of vitamin K deficiency in male SPF-rats fed an irradiated semisynthetic diet (24% Soyprotein, 0.25% DL-Methionin, 48% Cornstarch, 10% Sucrose, 5% Soyoil and 7% Cellulose and a vitamin- and mineral mixture) with a vitamin K content of 0.63 mg/kg diet is reported including clinical symptoms, pathological findings, coagulation parameters and investigations of intestinal flora. The deficiency could be reproduced experimentally in SPF- and germfree male rats and prevented by vitamin K supplementation (K/sub 3/ in the water or K/sub 1/ parenterally). Monoassoziation with an E. coli strain as well as conventionalization of SPF-rats were effective to prevent deficiency symptoms. The significance of a stable intestinal flora for intestinal vitamin K synthesis is emphasized. Nutrients and their influence on the intestinal flora are discussed with special reference to the mechanism of coprophagy, which makes intestinal vitamin K synthesis available to the rat.

Vitamin K deficiency in SPF-rats fed a semisynthetic irradiated diet

International Nuclear Information System (INIS)

Juhr, N.C.; Dietzel, L.; Horn, J.

1975-01-01

A case of vitamin K deficiency in male SPF-rats fed an irradiated semisynthetic diet (24% Soyprotein, 0.25% DL-Methionin, 48% Cornstarch, 10% Sucrose, 5% Soyoil and 7% Cellulose and a vitamin- and mineralmixture) with a vitamin K content of 0.63 mg/kg diet is reported including clinical symptoms, pathological findings, coagulation parameters and investigations of intestinal flora. The deficiency could be reproduced experimentally in SPF- and germfree male rats and prevented by vitamin K supplementation (K 3 in the water or K 1 parenterally). Monoassoziation with an E. coli strain as well as conventionalization of SPF-rats were effective to prevent deficiency symptoms. The significance of a stable intestinal flora for intestinal vitamin K synthesis is emphasized. Nutrients and their influence on the intestinal flora are discussed with special reference to the mechanism of coprophagy, which makes intestinal vitamin K synthesis available to the rat

Características ultra-estruturais do nó sinoatrial de rato Wistar Superstructural features of the wistar strain male rats' sinoatrial node (SAN

Directory of Open Access Journals (Sweden)

Carlos Alberto Mandarim de Lacerda

2002-04-01

Full Text Available As características ultra-estruturais do nó sinoatrial (NSA de 5 ratos machos da variedade Wistar, com 3 meses de idade, foram estudadas por meio de microscopia eletrônica de transmissão (MET. Fragmento pequeno, contendo a região do NSA e área adjacente do átrio direito do coração, foi retirado e fixado em glutaraldeído 2,5% e processado de acordo com técnica convencional para MET. A morfologia do nó sinoatrial de ratos é semelhante a de outros mamíferos. O NSA é uma estrutura anatômica independente do miocárdio atrial, constituído por células típicas (miócitos nodais, células de transição e, principalmente, células nodais imersos em matriz extracelular, na qual predominam fibras colágenas, fibroblastos e nervosThe superstructural features of five Wistar strain male rats' sinoatrial node (SAN at 3-mo-old were studied through transmission electron microscopy (TEM. Small fragments with the regions containing the SAN were cut off, fixed in glutaraldehyde 2.5% and processed according to the conventional technique for TEM. The morphology of the sinoatrial node of the rats is similar as found in other mammals. The SAN is an independent anatomic structure of the atrial myocardial, constituted of typical cells (nodal myocytes, transition cells and nodal cells principally immersed in the extra cellular matrix where collagen fibers, fibroblasts and nerve predominate

Behavior of lactobacilli isolated from fermented slurry (ben-saalga in gnotobiotic rats.

Directory of Open Access Journals (Sweden)

Williams Turpin

Full Text Available Most bacterial strains, which have been studied so far for their probiotic functions, are extensively used by manufacturers in developed countries. In our work, we sought to study a mix (called BSL comprising three strains belonging to Lactobacillus fermentum, L. paraplantarum and L. salivarius, that were isolated from a traditional African pearl millet based fermented slurry. Our objective was to study this BSL cocktail in gnotobiotic rats, to evaluate their survival and their behavior in the digestive tract conditions. After a single oral inoculation of germfree rats with BSL, the species established stably in the digestive tract with the following hierarchy of abundance: L. salivarius> L. plantarum> L. fermentum. BSL cocktail was metabolically active since it produced 50 mM lactate and it expressed genes involved in binding mechanism in the caecum. Furthermore, the global morphology of the colon epithelium was not disturbed by the BSL cocktail. BSL cocktail did not modify mucus content and host mucus-related genes (MUC1, MUC2, MUC3 or resistin-like molecule β. The cocktail of lactobacilli enhanced the proliferating cell nuclear antigen (PCNA at a level comparable to what was observed in conventional rats. PCNA was involved in proliferation and DNA repair, but the presence of the cocktail did not provoke proliferative events (with Ki67 as indicator, so we suppose BSL may help gut preservation. This work is the first step towards the selection of strains that are derived from traditional fermented food to formulate new probiotic mixture.

Effect ofPunica granatum peel extract on learning and memory in rats

Institute of Scientific and Technical Information of China (English)

Shalini Adiga; Prabhav Trivedi; Ravichandra V; Debashree Deb; Forum Mehta

2010-01-01

Objective:To evaluate potential memory enhancing effect ofPunica granatum peel extract on rats.Methods: Healthy adult male albino rats of Wistar strain were used. Each group of6 rats were administered either distilled water or50mg/kg of extract or100 mg/kg of extract for 15days and subjected to passive avoidance test or T-maze test. In the next phase rats were administered distilled water or100 mg/kg of extract for15 days and the rats were given injection diazepam before subjecting them to the tests.Results:The overall performance was better in test groups compared to control groups. Among the test groups,100 mg/kg rats performed better than50mg/kg. The effect on spatial learning parameters like mean number of alternations and mean percentage bias was more marked compared to retention testing parameters like latency. 100 mg/kg Punica extract treated group also improved performance of diazepam treated rats. Conclusions:There is a definite trend of memory improvement byPunica granatum peel with effects being more marked on spatial learning tendency and long term memory than on retention capacity.

Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

International Nuclear Information System (INIS)

Pollak, R.; Blanchard, J.M.; Lazda, V.A.

1986-01-01

Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs

Studies on colon cancer prone rats. Spontaneous small intestinal carcinomas and tumor induction of small intestine by x-irradiation

Energy Technology Data Exchange (ETDEWEB)

Maeura, Y [Osaka Univ. (Japan). Faculty of Medicine

1979-12-01

Histological investigation was carried out for Wister-Furth (WF) rats, prone to cancers of the colon and small intestine. Gastric cancer was observed in about 1/4 of the rats with the cancers of the colon and the small intestine, indicating that these rats could be the model animals of the cancer family syndrome with multi-cancers in the gastrointestinal tracts. The small intestine of WF and SD (Sprague-Dowley) rats as exposed to 1000, 2 x 1000, 1500, and 2000 R of x-rays at a dose rate of 157 R/min. In each group the stomach, small intestine, cecum, and colon were histologically investigated, immediately and 15, 25, and 35 weeks after irradiation. The rates of cancer occurrence in 15, 25, and 35 weeks were 5/17, 9/19, and 9/14 for WF strain and 1/8, 2/7, and 2/8 for SD strain, respectively. The rate increased with the increment of the days after irradiation. It was suggested that the atypical epithelium of the gastrointestinal tracts induced the cancer in high rates when some trigger was added.

A noninvasive method to study regulation of extracellular fluid volume in rats using nuclear magnetic resonance

Data.gov (United States)

U.S. Environmental Protection Agency — NMR fluid measurements of commonly used rat strains when subjected to SQ normotonic or hypertonic salines, as well as physiologic comparisons to sedentary and...

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

Science.gov (United States)

Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

2012-09-01

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii.

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Kimberly M Cirelli

2014-03-01

Full Text Available Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing Nlrp1. This gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (LT induced rapid cell death (pyroptosis. We show here that rat strain differences in Toxoplasma infected macrophage sensitivity to pyroptosis, IL-1β/IL-18 processing, and inhibition of parasite proliferation are perfectly correlated with NLRP1 sequence, while inversely correlated with sensitivity to anthrax LT-induced cell death. Using recombinant inbred rats, SNP analyses and whole transcriptome gene expression studies, we narrowed the candidate genes for control of Toxoplasma-mediated rat macrophage pyroptosis to four genes, one of which was Nlrp1. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages resulted in higher parasite replication and protection from cell death. Reciprocally, overexpression of the NLRP1 variant from Toxoplasma-sensitive macrophages in pyroptosis-resistant cells led to sensitization of these resistant macrophages. Our findings reveal Toxoplasma as a novel activator of the NLRP1 inflammasome in rat macrophages.

A new nonlinear parameter in the developed strain-to-applied strain of the soft tissues and its application in ultrasound elasticity imaging.

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Xu, Jingping; Tripathy, Sakya; Rubin, Jonathan M; Stidham, Ryan W; Johnson, Laura A; Higgins, Peter D R; Kim, Kang

2012-03-01

Strain developed under quasi-static deformation has been mostly used in ultrasound elasticity imaging (UEI) to determine the stiffness change of tissues. However, the strain measure in UEI is often less sensitive to a subtle change of stiffness. This is particularly true for Crohn's disease where we have applied strain imaging to the differentiation of acutely inflamed bowel from chronically fibrotic bowel. In this study, a new nonlinear elastic parameter of the soft tissues is proposed to overcome this limit. The purpose of this study is to evaluate the newly proposed method and demonstrate its feasibility in the UEI. A nonlinear characteristic of soft tissues over a relatively large dynamic range of strain was investigated. A simplified tissue model based on a finite element (FE) analysis was integrated with a laboratory developed ultrasound radio-frequency (RF) signal synthesis program. Two-dimensional speckle tracking was applied to this model to simulate the nonlinear behavior of the strain developed in a target inclusion over the applied average strain to the surrounding tissues. A nonlinear empirical equation was formulated and optimized to best match the developed strain-to-applied strain relation obtained from the FE simulation. The proposed nonlinear equation was applied to in vivo measurements and nonlinear parameters were further empirically optimized. For an animal model, acute and chronic inflammatory bowel disease was induced in Lewis rats with trinitrobenzene sulfonic acid (TNBS)-ethanol treatments. After UEI, histopathology and direct mechanical measurements were performed on the excised tissues. The extracted nonlinear parameter from the developed strain-to-applied strain relation differentiated the three different tissue types with 1.96 ± 0.12 for normal, 1.50 ± 0.09 for the acutely inflamed and 1.03 ± 0.08 for the chronically fibrotic tissue. T-tests determined that the nonlinear parameters between normal, acutely inflamed and fibrotic tissue

Collagen changes in the cochlea of aged Fischer 344 rats

Czech Academy of Sciences Publication Activity Database

Buckiová, Daniela; Popelář, Jiří; Syka, Josef

2006-01-01

Roč. 41, - (2006), s. 296-302 ISSN 0531-5565 R&D Projects: GA ČR GA309/04/1074; GA MZd NR8113; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Presbycusis * Rat * Fischer 344 strain Subject RIV: FH - Neurology Impact factor: 2.930, year: 2006

Vitamin C deficiency exerts paradoxical cardiovascular effects in osteogenic disorder Shionogi (ODS) rats.

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Vergely, Catherine; Goirand, Françoise; Ecarnot-Laubriet, Aline; Renard, Céline; Moreau, Daniel; Guilland, Jean-Claude; Dumas, Monique; Rochette, Luc

2004-04-01

Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac and vascular variables and reperfusion arrhythmias. For this purpose, we used a mutant strain of Wistar rats, osteogenic disorder Shionogi (ODS). After 15 d of consuming a vitamin C-deficient diet, ODS rats had a 90% decrease in plasma and tissue levels of ascorbate compared with ODS vitamin C-supplemented rats and normal Wistar rats. However, plasma antioxidant capacity, proteins, alpha-tocopherol, urate, catecholamines, lipids, and nitrate were not influenced by the vitamin C deficiency in ODS rats. Moreover, there was no difference between ODS vitamin C-deficient and -supplemented rats in heart rate and arterial pressure. After 5 min of an in vivo regional myocardial ischemia, various severe arrhythmias were observed, but their intensities were not modified by vitamin C in vitamin C-deficient ODS rats. The vascular reactivity, measured in vitro on thoracic arteries, was not altered by ascorbate deficiency in ODS rats. These unexpected results suggest that unidentified compensatory mechanisms play a role in maintaining normal cardiac function and vascular reactivity in vitamin C-deficient rats.

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

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Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

2012-12-01

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

International Nuclear Information System (INIS)

Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

2012-01-01

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats.

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Siva Sankara Vara Prasad Sakamuri

Full Text Available BACKGROUND: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1 regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. METHODOLOGY/PRINCIPAL FINDINGS: Subcutaneous injection of CBX (50 mg/kg body weight or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment. Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.

Comparison of CYP2D metabolism and hepatotoxicity of the myocardial metabolic agent perhexiline in Sprague-Dawley and Dark Agouti rats.

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Licari, Giovanni; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

2015-01-01

1. Perhexiline, a chiral anti-anginal agent, may be useful to develop new cardiovascular therapies, despite its potential hepatotoxicity. 2. This study compared Dark Agouti (DA) and Sprague-Dawley (SD) rats, as models of perhexiline's metabolism and hepatotoxicity in humans. Rats (n = 4/group) received vehicle or 200 mg/kg/d of racemic perhexiline maleate for 8 weeks. Plasma and liver samples were collected to determine concentrations of perhexiline and its metabolites, hepatic function and histology. 3. Median (range) plasma and liver perhexiline concentrations in SD rats were 0.09 (0.04-0.13) mg/L and 5.42 (0.92-8.22) ng/mg, respectively. In comparison, DA rats showed higher (p < 0.05) plasma 0.50 (0.16-1.13) mg/L and liver 24.5 (9.40-54.7) ng/mg perhexiline concentrations, respectively, 2.5- and 3.7-fold higher cis-OH-perhexiline concentrations, respectively (p < 0.05), and lower plasma metabolic ratio (0.89 versus 1.55, p < 0.05). In both strains, the (+):(-) enantiomer ratio was 2:1. Perhexiline increased plasma LDH concentrations in DA rats (p < 0.05), but had no effect on plasma biochemistry in SD rats. Liver histology revealed lower glycogen content in perhexiline-treated SD rats (p < 0.05), but no effects on lipid content in either strain. 4. DA rats appeared more similar to humans with respect to plasma perhexiline concentrations, metabolic ratio, enantioselective disposition and biochemical changes suggestive of perhexiline-induced toxicity.

Suramin-restricted blood volume in the placenta of normal and diabetic rats is normalized by vitamin E treatment.

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Nash, P; Eriksson, U J

2007-01-01

Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one

Cross-fostering does not alter the neurochemistry or behavior of spontaneously hypertensive rats

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Russell Vivienne A

2009-06-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR, displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY. The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam. Methods SHR/NCrl (Charles River, USA, WKY/NCrl (Charles River, USA and Sprague Dawley rats (SD/Hsd, Harlan, UK were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2. Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices. Results There was no significant effect of "strain of dam" but there was a significant effect of "pup strain" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus

Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

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Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

1983-01-01

Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats

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Jana eBurianová

2015-03-01

Full Text Available In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC, medial geniculate body (MGB and auditory cortex (AC in rats (strains Long Evans and Fischer 344 and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive(-ir neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex (VC of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

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Xuefeng Ren

Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

The Activity Test of Ethanol Extract Tea Parasite Herb (Scurrulla Artopurpurea) as an Immunostimulator on Wistar Strain Rat Sensititized with Sheep Red Blood Cell

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Yulianti, Retno; Dimas A, M.; Hafiz, Aldi; Amalia, Muttia

2018-03-01

Tea parasite (Scurrulla artropurpurea) is one of the hemiparasite plants suspected as an imustimulator agent. The aims of this study was to prove the activity of tea parasite herb extract as immunostimulator in Wistar strain rats that are sensitized by sheep red blood cell suspension (SRBC). Twenty eight Wistar rats were divided into 4 groups. The control group was given CMC 1%, the treatment group was given the tea parasite herb extract at doses of 750 mg, 1.5g and 3 g/kgBW/day, each group was sensitized by SRBC 10% as much 0.5 ml intraperitoneally on the 0th and 9th days and 0.1 ml intraplantar on 12th days. The total number of leukocyte and lymphocyte cells was performed using blood smear and analyzed by GLMRM. test. The macrophage cell activity and the capacity of the peritoneal fluid preparation on day 14 and analyzed by ANOVA test. The histopathological features are demonstrated after 48 hours of intraplantar injection, quantitatively perceived perivascular and periadnexal infiltrates. The results showed that there were average differences on leukocyte cell counts (F = 46.249) and total lymphocyte cells (F = 58.144) on each calculation (day), but there were no average differences between each treatment group. The highest activity of phagocytosis is 78% and continues to increase along with the additional dose of extract, without the increased capacity of macrophage phagocytosis. Histopathological features of slow-type IV reaction shows mild severity. It can be concluded that the active compound of the extract tea parasite herbare able to improve immune system.

Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer's Disease induced Albino Rats.

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Nimgampalle, Mallikarjuna; Kuna, Yellamma

2017-08-01

Alzheimer's disease is a type of dementia, and till now there is no suitable drug available for the complete cure of this disease. Now-a-days Probiotics, Lactobacillus strains play a therapeutic role in cognitive disorders through Gut-Brain Axis communication. The present study was aimed to evaluate the anti-Alzheimer properties of Lactobacillus plantarum MTCC1325 against D-Galactose-induced Alzheimer's disease in albino rats. Healthy rats (48) of wistar strain were divided into four groups viz., Group-I: control rats received saline, Group-II: rats received intraperitoneal injection of D-Galactose (120 mg/kg body weight) throughout experiment, Group-III: initially animals were subjected to D-Galactose injection for six weeks, then followed by simultaneously received both D-Galactose and L. plantarum MTCC1325 (12×10 8 CFU/ml; 10 ml/kg body weight) for 60 days and Group-IV: rats which were orally administered only with Lactobacillus plantarum MTCC1325 for 60 days. During the experimentation, both morphometric and behavioural aspects were studied. Later we have examined histopathological changes and estimated cholinergic levels in selected brain regions of all experimental groups of rats including control on selected days. Morphometric, behavioural changes, ACh levels were significantly decreased and pathological hallmarks such as amyloid plaques and tangles were also observed in AD model group. Treatment of AD-group with L. plantarum MTCC1325 for 60 days, not only ameliorated cognition deficits but also restored ACh and the histopathological features to control group. However, no significant effects have been observed in the group treated with L. plantarum alone. The study revealed that, L. plantarum MTCC1325 might have anti-Alzheimer properties against D-Galactose induced Alzheimer's disease.

Milk improved the metabolic syndrome in obese ß rats

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María Catalina Olguin

2014-02-01

Full Text Available The response of adult spontaneously obese rats from the IIMb/Beta strain fed a high calcium skimmed milk diet (MHCa, high calcium from carbonate (HCa and a normal AIN 93 diet during 45 days was evaluated. Body weight, food intake and fecal fat excretion were measured. At the end of the experiment rats were euthanized, abdominal fat pads and livers were excised and weighed. Blood and liver triacylglycerols, total cholesterol and fractions were quantified. Body weight increase and abdominal fat pads in the MHCa group were significantly lower than in the other two. Plasma triacylglycerols, total and LDL-cholesterol were diminished in the MHCa group. Fecal lipid excretion was increased in the adult MHCa group. Total liver lipids and triacylglycerols showed a significant diminution in the MHCa group. These results suggest that calcium and other bioactive compounds from milk, most probably present in whey fraction, and not calcium carbonate exerted an "anti-obesity" effect on these rats.

Acute toxicity testing of some herbicides-, alkaloids-, and antibiotics-metabolizing soil bacteria in the rat.

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Kaiser, A; Classen, H G; Eberspächer, J; Lingens, F

1981-01-01

Seven strains of soil bacteria with the ability to metabolize herbicides, alkaloids or antibiotics were tested in rats for acute toxicity. 1. Upon oral administration of 9.0 x 10(8) to 6.6 x 10(10) cells daily during 7 d no adverse reactions were observed. 2. Exposure by air did not lead to specific pulmonary changes. 3. Intracutaneous injection of 7.5 x 10(6) to 1.4 x 10(8) cells did not lead to adverse skin reactions. 4. Intraperitoneal injections up to 10(8) cells per animal did not kill rats although bacteria entered blood. At higher concentrations some mortality occurred partly due to unspecific stress reactions. 5. Animal data and observations on 20 humans being exposed to these strains for 2 months up to 15 years support the view that the bacteria tested are essentially harmless for health.

Aversive properties of negative incentive shifts in Fischer 344 and Lewis rats

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Brewer, Adam; Johnson, Patrick; Stein, Jeff; Schlund, Michael; Williams, Dean C.

2018-01-01

Research on incentive contrast highlights that reward value is not absolute but rather is based upon comparisons we make to rewards we have received and expect to receive. Both human and nonhuman studies on incentive contrast show that shifting from a larger more-valued reward to a smaller less-valued reward is associated with long periods of nonresponding—a negative contrast effect. In this investigation, we used two different genetic rat strains, Fischer 344 and Lewis rats that putatively differ in their sensitivity to aversive stimulation, to assess the aversive properties of large-to-small reward shifts (negative incentive shifts). Additionally, we examined the extent to which increasing cost (fixed-ratio requirements) modulates negative contrast effects. In the presence of a cue that signaled the upcoming reward magnitude, lever pressing was reinforced with one of two different magnitudes of food (large or small). This design created two contrast shifts (small-to-large, large-to-small) and two shifts used as control conditions (small-to-small, large-to-large). Results showed a significant interaction between rat strain and cost requirements only during the negative incentive shift with the emotionally reactive Fischer 344 rats exhibiting significantly longer response latencies with increasing cost, highlighting greater negative contrast. These findings are more consistent with emotionality accounts of negative contrast and results of neurophysiological research that suggests shifting from a large to a small reward is aversive. Findings also highlight how subjective reward value and motivation is a product of gene-environment interactions. PMID:27864048

Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats

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Sanapareddy Nina

2010-02-01

Full Text Available Abstract Background Experimental models of pulmonary embolism (PE that produce pulmonary hypertension (PH employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD and Copenhagen (Cop rats can produce persistent PH. Methods blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Results Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours and 97% (5 days in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days. Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Conclusions Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.

Spontaneous and x-irradiation induced carcinomas of small intestine in Wistar-Furth rats

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Maeura, Y; Kosaki, G; Kitamura, H [Osaka Univ. (Japan). Faculty of Medicine; Nagatomo, T

1980-04-01

Spontaneous carcinoma of the small intestine in Wistar-Furth (WF) rats and carcinoma of the small intestine induced by local x-ray irradiation to the abdomen of WF rats without carcinoma were observed, and x-ray sensitivity of the small intestine mucosa was reported. Out of 19 rats with spontaneous carcinoma of the small intestine, 18 also had carcinoma of the colon, and 4 also had gastric cancer. They already had spontaneous carcinoma of the small intestine within 2 weeks after their birth, and the ratio of female and male was 13 : 6. Histological type of this carcinoma in all 19 rats was highly differentiated adenocarcinoma, and small intestine epithelium around carcinoma presented atypical epithelium. As to mice without carcinoma, x-ray, 1,000 R, 1,500 R, and 2,000 R, was irradiated to the abdomen of Sprague-Dawley (SD) and WF rats. In the irradiation with 1,000 R, carcinogenesis was not found in rats of both strains. In the irradiation with 1,500 R, carcinogenesis was hardly found, but in the irradiation with 2,000 R, carcinoma of small intestine occurred in 5 of 17 rats 15 weeks after the irradiation, 9 of 19 rats 25 weeks after the irradiation, and 9 of 14 rats 35 weeks after the irradiation. Histological type of carcinoma in irradiated rats was highly differentiated adenocarcinoma. The incidence of carcinoma in irradiated rats was higher in WF rats than SD rats through the course after the irradiation, which suggested that x-ray sensitivity of WF rats was higher than that of SD rats. Therefore, carcinoma of the small intestine in irradiated mice seemed to be induced by x-ray.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

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Attakpa, E S; Bertin, G A; Chabi, N W; Ategbo, J-M; Seri, B; Khan, N A

2017-11-24

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

[Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)].

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Ticca, M

1976-01-01

The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.

Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset hydrocephalus are influenced by gender and genetic background

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Mayorga David A

2005-06-01

Full Text Available Abstract Background The LEW/Jms rat strain has inherited hydrocephalus, with more males affected than females and an overall expression rate of 28%. This study aimed to determine chromosomal positions for genetic loci causing the hydrocephalus. Methods An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F × L × L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L × (L × F], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER. Results The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %, but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ventricle-to-brain width ratio, was ranked as B group Conclusion Phenotypic expression of hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and possibly two chromosomal regions are associated with the hydrocephalus.

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

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Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

2016-07-01

Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Reference curves for assessing the physical growth of male Wistar rats].

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Cossio-Bolaños, Marco; Gómez Campos, Rossana; Vargas Vitoria, Rodrigo; Hochmuller Fogaça, Rosalvo Tadeu; de Arruda, Miguel

2013-11-01

Wistar rats are one of the most popular strains routinely used for research in the laboratory to serve as an important research tool, so it requires strict control of variables such as age, sex and body weight, and Thus to extrapolate the results to the human model. To develop reference curves for assessing the physical growth of male Wistar rats according to chronological age and somatic maturation from a non-invasive. The subjects studied were 731 male Wistar rats transversely. We assessed age, body weight and body surface. LMS method was used to construct percentile curves based on weight and somatic maturation. The proposed physical growth curves are used to track the physical growth and nutritional status diagnosis of male Wistar rats. Budgets by cutting points are: P3, P10, P25, P50, P75, P90 and P97. The results suggest that scientists from different areas can use such references, in order to extrapolate somatic growth phases of the laboratory rat and the human model is a non-invasive alternative to assess growth and nutritional status. Copyright AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

International Nuclear Information System (INIS)

Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

1980-01-01

Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

Gene Expression in Accumbens GABA Neurons from Inbred Rats with Different Drug-Taking Behavior

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Sharp, B.M.; Chen, H.; Gong, S.; Wu, X.; Liu, Z.; Hiler, K.; Taylor, W.L.; Matta, S.G.

2011-01-01

Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration; Lewis rats operantly self-administer drugs of abuse including nicotine, whereas Fisher self-administer poorly. As shown herein, operant food self-administration is similar. Based on their pivotal role in drug reward, we hypothesized that differences in basal gene expression in GABAergic neurons projecting from nucleus accumbens (NAcc) to ventral pallidum (VP) play a role in vulnerability to drug taking behavior. The transcriptomes of NAcc shell-VP GABAergic neurons from these two strains were analyzed in adolescents, using a multidisciplinary approach that combined stereotaxic ionotophoretic brain microinjections, laser-capture microdissection (LCM) and microarray measurement of transcripts. LCM enriched the gene transcripts detected in GABA neurons compared to the residual NAcc tissue: a ratio of neuron/residual > 1 and false discovery rate (FDR) 3 yielded 3,514. Strain-dependent differences in gene expression within GABA neurons were identified; 322 vs. 60 transcripts showed 1.5-fold vs. 2-fold differences in expression (FDR<5%). Classification by gene ontology showed these 322 transcripts were widely distributed, without categorical enrichment. This is most consistent with a global change in GABA neuron function. Literature-mining by Chilibot found 38 genes related to synaptic plasticity, signaling and gene transcription, all of which determine drug-abuse; 33 genes have no known association with addiction or nicotine. In Lewis rats, upregulation of Mint-1, Cask, CamkIIδ, Ncam1, Vsnl1, Hpcal1 and Car8 indicates these transcripts likely contribute to altered signaling and synaptic function in NAcc GABA projection neurons to VP. PMID:21745336

Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet

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Neus Martínez-Micaelo

2016-10-01

Full Text Available Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY and Lewis (LEW show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2 as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity.

Morphometric golgi study of some cortical locations in wag/rij and aci rat strains

NARCIS (Netherlands)

Karpova, A.V.; Bikbaev, A.F.; Coenen, A.M.L.; Luijtelaar, E.L.J.M. van; Luijtelaar, E.L.J.M. van; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.

2004-01-01

The present study was aimed to investigate the neuronal organization of two neocortical frontal zones using a Golgi staining technique in genetic epileptic rats, WAG/Rij's. One cortical zone was a specific part of the somatosensory cortex, which was recently proposed to contain a cortical epileptic

Caloric Restriction in Lean and Obese Strains of Laboratory Rat: Effects on Body Composition, Metabolism, Growth, and Overall Health

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NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improv...

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

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Zhao J

2017-12-01

Full Text Available Jingbo Zhao,1 Jian Yang,1 Donghua Liao,1 Hans Gregersen2 1Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Giome Center, Department of Surgery, Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, Hong Kong Background: Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective: We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design: Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR, and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results: Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05. The stress relaxed less in the diabetic intestinal segment (P<0.05. Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion: Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. Keywords: afferents, spike rate, stress–strain, creep

Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat.

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Christelle Veyrat-Durebex

Full Text Available The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3 ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3, known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF and thyrotropin-releasing hormone (TRH.

Pengaruh Lama Pemberian Diet Tinggi Kolesterol terhadap Kadar LDL dan TGF-Β Serum Tikus Putih (Rattus novergicus strain Wistar

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Biomechy Oktomalioputri

2016-01-01

to observe the effect of duration of giving  high-cholesterol diet on Low Density Lipoprotein and Transforming Growth Factor β levels white rats (Rattus novergicus Wistar strain. This study uses  post-test only control group design, carried out on male rats Rattus novergicus 3-4 months, weight 200-250 grams. The study sample consisted of 24 rats were divided into 4 groups: control group, group A, group B and group C. Except  the control group, the group of rats given a high-cholesterol diet in the form of goat fat 10%, 5% quail eggs for 10 days to group A, group B for 20 days and 30 days for group C. At the end of the experiment blood was taken and examined LDL and TGF-β levels. Results were analyzed using bivariate. The analysis is oneway Anova test. The results of research known to have effect of duration on giving high-cholesterol diet to increase serum LDL levels of rats with p = 0.01 (p<0.05. This is the same case with TGF-β, which there was effect of duration on giving high-diet cholesterol diet to decrease serum TGF-β levels of rats where p = 0.04 (p>0.05. This study concludes that there are effect of duration on giving high-cholesterol diet to levels of LDL and TGF-β white rats Rattus novergicus Wistar strain.Keywords:  high-cholesterol diet, LDL, TGF β

Developmental Exposure to an Environmental PCB Mixture ...

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Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to evaluate the effect of developmental exposure to an environmentally relevant PCB mixture on seizure susceptibility in the rat. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of the PCB mixture dissolved in corn oil vehicle during the perinatal period. On postnatal day (PND) 21, pups were weaned, and two males from each litter were randomly selected for the kindling study. As adults, the male rats were implanted bilaterally with electrodes in the basolateral amygdala. For each animal, afterdischarge (AD) thresholds in the amygdala were determined on the first day of testing followed by once daily stimulation at a standard 200 µA stimulus intensity until three stage 5 generalized seizures (GS) ensued. Developmental PCB exposure did not affect the AD threshold or total cumulative AD duration, but PCB exposure did increase the latency to behavioral manifestations of seizure propagation. PCB exposed animals required significantly more stimulations to reach stage 2 seizures compared to control animals, indicating an attenuated focal (amygdala) excitability. A delay in kindling progression from a focally stimulated limbic site stands in contrast to our previous finding of increase

Entrainment of Spontaneously Hypertensive Rat Fibroblasts by Temperature Cycles

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Sládek, Martin; Sumová, Alena

2013-01-01

The functional state of the circadian system of spontaneously hypertensive rats (SHR) differs in several characteristics from the functional state of normotensive Wistar rats. Some of these changes might be due to the compromised ability of the central pacemaker to entrain the peripheral clocks. Daily body temperature cycles represent one of the important cues responsible for the integrity of the circadian system, because these cycles are driven by the central pacemaker and are able to entrain the peripheral clocks. This study tested the hypothesis that the aberrant peripheral clock entrainment of SHR results from a compromised peripheral clock sensitivity to the daily temperature cycle resetting. Using cultured Wistar rat and SHR fibroblasts transfected with the circadian luminescence reporter Bmal1-dLuc, we demonstrated that two consecutive square-wave temperature cycles with amplitudes of 2.5°C are necessary and sufficient to restart the dampened oscillations and entrain the circadian clocks in both Wistar rat and SHR fibroblasts. We also generated a phase response curve to temperature cycles for fibroblasts of both rat strains. Although some of the data suggested a slight resistance of SHR fibroblasts to temperature entrainment, we concluded that the overall effect it too weak to be responsible for the differences between the SHR and Wistar in vivo circadian phenotype. PMID:24116198

Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse pep-3 (Dip-1) and human PEP-c.

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Womack, J E; Cramer, D V

1980-10-01

Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).

Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats.

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Meyer, Andrew C; Bardo, Michael T

2015-07-01

Previous research suggests both genetic and environmental influences on substance abuse vulnerability. The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). "Addiction-prone" LEW rats had greater acquisition of amphetamine self-administration on a FR1 schedule compared to "addiction-resistant" F344 rats when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW rats. While no group differences were obtained in extracellular DA, gene × environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW rats. The current results demonstrate gene × environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral and neurochemical differences were not related directly, indicating that

Hormones of thyroid gland in sera of rats treated with different dose of concentrated potassium iodine solutions

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Marković Ljiljana

2010-01-01

Full Text Available Introduction Potassium iodine (KI is used as a drug therapy for treating numerous diseases such as small-vessel vasculitis, erythema nodosum, vasculitis nodularis, Sweet's syndrome, tuberculosis and granulomatosis, and for iodized salt. At the same time, KI can be harmful. Iodine intake may increase the frequency of thyroiditis in humans, and may induce the occurrence of experimental thyroiditis (ET in animals. Investigations on an experimental model for the examination of thyroiditis in Wistar rats have clearly showed morphological changes in the rat thyroid evoked by KI administration. Objective The purpose of this study was to compare the effects of low and high doses of KI on the thyroid gland of Wistar rats and determine the effect on hormone status (T4, T3 and TSH in this rat strain. Methods Two groups of rats from the Wistar strain were treated with a low iodine dose (225 μg/g BW and with a high iodine dose (675 μg/g BW of KI solutions. Untreated nonimmunized animals served as controls. The solution was administrated daily intraperitoneally during the period of 26 consecutive days. Results Monitoring hormone status (TSH, T3 and T4 and morphological changes it was found that therapeutic doses of KI applied in treatment induced the occurrence of experimental thyroiditis (chronic destructive Hashimoto's thyroiditis in humans and cell necrosis in animals not carrying a genetic susceptibility. Significant inflammatory changes were observed in rats treated with a high iodine dose. Conclusion The early iodine induced cell necrosis and inflammation in the nonimmunized animals without genetic susceptibility is a new experimental model of thyroiditis. .

RatMap--rat genome tools and data.

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Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

RatMap—rat genome tools and data

Science.gov (United States)

Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

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T.T. Rosa

1995-03-01

Full Text Available The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v -63% and excretion ofsodium (-57% v-79% were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51% than in controls (-39%. Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerularfiltration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

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Wu Xianli

2009-09-01

Full Text Available Abstract Background Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB on formation of aberrant crypt foci (ACF in colons of male Fisher F344 rats (inbred strain. However, effects of BB on colon tumors and in both genders are unknown. Methods We examined efficacy of BB in inhibition of azoxymethane (AOM-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain. Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. Results Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P P P > 0.05 to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1 by BB. There was a tendency (0.1 > P > 0.05 for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P P Conclusion Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma by BB.

Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.

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Gear, R B; Yan, M; Schneider, J; Succop, P; Heffelfinger, S C; Clegg, D J

2007-10-04

Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The "window of susceptibility" to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this "window". We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CD(R) IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

Beta-Blockers: An Abstracted Bibliography.

Science.gov (United States)

1989-04-04

B. S. TITLE: Ocular Effects of Acebutolol and Propranolol. REFERENCE: Metabolic, Pediatric an( Systemic Ophthalmology, Vol. 4, pp. 87-88, DRUGS...PROCEDURES-: Tested for drug influence on barbiturate hypnosis, anialgesia, anticonvulsant effect, metrazol convulsions, strychnine convulsions, audiogenic

Mechanisms of Comorbidities Associated With the Metabolic Syndrome: Insights from the JCR:LA-cp Corpulent Rat Strain.

Science.gov (United States)

Diane, Abdoulaye; Pierce, W David; Kelly, Sandra E; Sokolik, Sharon; Borthwick, Faye; Jacome-Sosa, Miriam; Mangat, Rabban; Pradillo, Jesus Miguel; Allan, Stuart McRae; Ruth, Megan R; Field, Catherine J; Hutcheson, Rebecca; Rocic, Petra; Russell, James C; Vine, Donna F; Proctor, Spencer D

2016-01-01

Obesity and its metabolic complications have emerged as the epidemic of the new millennia. The use of obese rodent models continues to be a productive component of efforts to understand the concomitant metabolic complications of this disease. In 1978, the JCR:LA-cp rat model was developed with an autosomal recessive corpulent ( cp ) trait resulting from a premature stop codon in the extracellular domain of the leptin receptor. Rats that are heterozygous for the cp trait are lean-prone, while those that are homozygous ( cp/cp ) spontaneously display the pathophysiology of obesity as well as a metabolic syndrome (MetS)-like phenotype. Over the years, there have been formidable scientific contributions that have originated from this rat model, much of which has been reviewed extensively up to 2008. The premise of these earlier studies focused on characterizing the pathophysiology of MetS-like phenotype that was spontaneously apparent in this model. The purpose of this review is to highlight areas of recent advancement made possible by this model including; emerging appreciation of the "thrifty gene" hypothesis in the context of obesity, the concept of how chronic inflammation may drive obesogenesis, the impact of acute forms of inflammation to the brain and periphery during chronic obesity, the role of dysfunctional insulin metabolism on lipid metabolism and vascular damage, and the mechanistic basis for altered vascular function as well as novel parallels between the human condition and the female JCR:LA-cp rat as a model for polycystic ovary disease (PCOS).

Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats

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Diaz Heijtz Rochellys

2006-05-01

Full Text Available Abstract Background Molecular genetic studies suggest the dopamine D1 receptor (D1R may be implicated in attention-deficit/hyperactivity disorder (ADHD. As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue. Methods We investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg, on motor behaviour and expression of the plasticity-associated gene, c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR, the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived. Results SHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increased c-fos mRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels of c-fos mRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum of SHR when compared to WKY rats

Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats

DEFF Research Database (Denmark)

Oliveras, Ignasi; Sánchez-González, Ana; Sampedro-Viana, Daniel

2017-01-01

acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RESULTS: RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical...... antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI...

Building Cre Knockin Rat Lines Using CRISPR/Cas9.

Science.gov (United States)

Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

2017-01-01

Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool. We have used CRISPR/Cas9 system to generate rat strains that carry Cre genes in different targeted gene loci by direct delivery of gRNAs/Cas9/donors into fertilized eggs. Here, we described a stepwise procedure for the generation of Cre knockin rat, including target site selection, RNA preparation, the construction of the template donor, pronuclear injection, and the genotyping of precise Cre insertion in F 0 rats. Taken together, the establishment of Cre knockin line can be achieved within 6 weeks.

Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus.

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Mira C Patel

Full Text Available In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68 among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus. Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49, along with the historical prototype Fermon strain (ATCC, to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines

In vitro uptake of 75Se-selenite by lens of young and adult rats

International Nuclear Information System (INIS)

Sladkova, J.; Ostadalova, I.; Babicky, A.; Obenberger, J.

1988-01-01

The uptake was observed of 75 Se-selenite by the lens in Wistar strain rats in adult animals, in 17-day old rats kept with their mothers and in prematurely weaned rats. Also measured was the excretion of 75 Se by the lens of young and adult rats following incubation in the medium with radioselenium. The metabolites were analysed which were discharged by the lens containing 75 Se. In Brattleboro rats the uptake of 75 Se-selenite was also measured by the lens in young and adult rats. The uptake of 75 Se-selenite by the lens in young Wistar rats was found to be 1.6 times higher than by the lens of adult rats and the time course of the radioselenium uptake was slightly different. In the lens of prematurely weaned rats no significant difference was found in the uptake of radioselenium after 4 hours as compared with rats of the same age kept with their mothers. In homozygous Brattleboro rats, a higher uptake of 75 Se-selenite was found as compared with both young and adult heterozygous rats. The time course and the quantity of 75 Se efflux from the lens of young and adult Wistar rats differed significantly after 0.5 hour of pre-incubation. From metabolites containing 75 Se excreted by the lens following preincubation, glutathione selenotrisulfide and a not yet accurately determined fraction with a large share of radioactivity were isolated. The stated results provide yet more proof that selenium cataract is a manifestation of the ontogenic dependence of selenium metabolism in the lens and in the entire organism. (author). 4 tabs., 30 refs

Threshold dose to developing central nerve system of rats and mice from prenatal exposure to tritiated water

International Nuclear Information System (INIS)

Zhou Xiangyan; Wang Bing; Gao Weimin; Lu Huimin

1999-01-01

Objective: To study the threshold dose to the developing central nerve system of rats and mice from prenatal exposure to tritiated water. methods: Pregnant adult C 57 BL/6J strain mice and Wistar strain rats were irradiated with beta-rays from HTO by a single intraperitoneal injection on the 12.5 th and 13 th days of gestation. The activities of HTO were 24.09, 48.18 and 144.54 ( x 10 4 Bq/g bw), respectively. Fifty-six parameters including postnatal growth, neutro-behavior, pathology of brain, neuropeptide contents, changes of hippocampal neurons, Ca 2+ conductance of hippocampal neurons etc were used to test the teratogenic threshold dose the lowest dose was different from that of the control). Results: Of the observed 56 parameters of rats and mice 80.4% indicated that the threshold doses for prenatal HTO exposure ranged from 0.030 Gy to 0.092 Gy, and the other 19.6% showed the threshold doses from 0.093 to 0.300 Gy. Conclusions: There exists threshold dose from the low level tritiated water irradiation of the developing central nerve system

Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats

NARCIS (Netherlands)

Groblewski, Peter A.; Zietz, Chad; Willuhn, Ingo; Phillips, Paul E. M.; Chavkin, Charles

2015-01-01

Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour cocaine self-administration sessions. Twenty-four hours after the last swim stress, cocaine valuation was assessed during a single-session threshold

Context-dependent differences in grooming behavior among the NIH heterogeneous stock and the Roman high- and low-avoidance rats.

Science.gov (United States)

Estanislau, C; Díaz-Morán, S; Cañete, T; Blázquez, G; Tobeña, A; Fernández-Teruel, A

2013-12-01

Grooming occurs during/after stress and seems to accompany dearousal. Here, grooming was investigated under testing situations involving different levels of aversiveness, taking advantage of differences among three rat strains in fearfulness/anxiety. Inbred Roman High Avoidance (RHA-I) rats are less anxious/fearful than inbred Roman Low Avoidance (RLA-I). The outbred genetically heterogeneous stock of rats (NIH-HS), which resembles the RLA-I in many behavioral traits, was also studied. Adult male rats (RLA-I: n=9, RHA-I: n=10, NIH-HS: n=12) were observed for 30min in: a novel open-field, a novel hole-board and in the home-cage. They were also observed during two-way active avoidance training. Differences in grooming depended on test situation: (a) No differences were found in the home-cage. (b) While tested in a novel environment, RHA-I showed less grooming activity than the other rats. (c) After avoidance responses appeared, differences among the strains were opposite to the observed in novelty tests. Furthermore, results suggest that (i) grooming is mostly suppressed when assured aversive experience is under way; (ii) rostral grooming prevails when experience with aversive stimuli is unpredictable (novelty) or potential (avoidance training); (iii) body grooming increases for a period in novel environments. In general, our results support that grooming takes place during dearousal. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

[Effect of NO-synthesis blockade on the free-radical processes in rats of different genetic strains with acute alloxan diabetes].

Science.gov (United States)

Belkina, L M; Terekhina, O L; Antipova, T A; Smirnova, E A; Kruglov, S V; Malyshev, I Iu

2013-11-01

Previously, we have shown that nitric oxide (NO) plays an important role in the pathogenesis of alloxan diabetes (ALD). In this study in August rats, with the congenital increased activity of NO, and in Wistar rats was induced ALD (130 mg/kg, p/c) and 15 days after were examined the effects of the NO-blockade synthesis, induced by administration of Nω-nitro-L-arginine (L-NNA) cour- se on the activity of lipid peroxidation (LP), HIF-1α level, the degree of NO-system activation. The activation of iNOS, HIF-1a expression and 3-nitrotyrosine accumulation in liver were more pronounced in August-ALD rats than in Wistar-ALD rats. The level of TBA-active products in the heart and liver was increased in both diabetic groups only in the first 3 days ofALD and then this indicator of LP sharply was decreased as compared with the control. This effect was pronounced more in August rats. The inhibition of NO overproduction reduced significantly the severity of ALD and prevented the activation of LP, iNOS and HIF-1a. Thus, these data suggest, that NO plays an important role in the pathogenesis of ALD and in the regulation of oxygen homeostasis.

Genetic maps of polymorphic DNA loci on rat chromosome 1

Energy Technology Data Exchange (ETDEWEB)

Ding, Yan-Ping; Remmers, E.F.; Longman, R.E. [National Institutes of Health, Bethesda, MD (United States)] [and others

1996-09-01

Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats.

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Marion Inostroza

Full Text Available Cognitive impairment is a major concern in temporal lobe epilepsy (TLE. While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA from two different rat strains (Wistar and Sprague-Dawley using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se.

A novel Dock8 gene mutation confers diabetogenic susceptibility in the LEW.1AR1/Ztm-iddm rat, an animal model of human type 1 diabetes

NARCIS (Netherlands)

Arndt, Tanja; Wedekind, Dirk; Jörns, Anne; Tsiavaliaris, Georgios; Cuppen, Edwin; Hedrich, Hans-Jürgen; Lenzen, Sigurd

2015-01-01

AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, arose through a spontaneous mutation within the inbred strain LEW.1AR1. A susceptibility locus (Iddm8) on rat chromosome 1 (RNO1) has been identified previously, which is accompanied by autoimmune diabetes and the

Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats.

Science.gov (United States)

Toropainen, Maija; Saarinen, Leena; Vidarsson, Gestur; Käyhty, Helena

2006-05-01

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c-) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c- rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.

Environmental enrichment ameliorates depressive-like symptoms in young rats bred for learned helplessness.

Science.gov (United States)

Richter, S Helene; Zeuch, Benjamin; Riva, Marco A; Gass, Peter; Vollmayr, Barbara

2013-09-01

The incidence of major depression is known to be influenced by both genetic and environmental factors. In the current study, we therefore set out to investigate depressive-like behavior and its modification by environmental enrichment using rats bred for 'learned helplessness'. 45 males of congenitally helpless (cLH, n=22) and non-helpless (cNLH, n=23) rats of two different generations were used to systematically investigate differential effects of environmental enrichment on learned helpless behavior, anhedonic-like behavior (sweetened condensed milk consumption) and spontaneous behavior in the home cage. While enrichment was found to reduce learned helpless behavior in 14 weeks old, but not 28 weeks old cLH rats, it did not affect the consumption of sweetened condensed milk. Regarding the home cage behavior, no consistent changes between rats of different strains, housing conditions, and ages were observed. We could thus demonstrate that a genetic predisposition for learned helplessness may interact with environmental conditions in mediating some, but not all depressive-like symptoms in congenitally learned helpless rats. However, future efforts are needed to isolate the differential benefits of environmental factors in mediating the different depression-related symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of Age and Exercise on the Viscoelastic Properties of Rat Tail Tendon

Science.gov (United States)

LaCroix, Andrew S.; Duenwald-Kuehl, Sarah E.; Brickson, Stacey; Akins, Tiffany L.; Diffee, Gary; Aiken, Judd; Vanderby, Ray; Lakes, Roderic S.

2013-01-01

Tendon mechanical properties are thought to degrade during aging but improve with exercise. A remaining question is whether exercise in aged animals provides sufficient regenerative, systemic stimulus to restore younger mechanical behaviors. Herein we address that question with tail tendons from aged and exercised rats, which would be subject to systemic effects but not direct loading from the exercise regimen. Twenty-four month old rats underwent one of three treadmill exercise training protocols for 12 months: sedentary (walking at 0° incline for 5 min/day), moderate (running at 0° incline for 30 min/day), or high (running at 4° incline for 30 min/day). A group of 9 month old rats were used to provide an adult control, while a group of 3 month old rats provided a young control. Tendons were harvested at sacrifice and mechanically tested. Results show significant age-dependent differences in modulus, ultimate stress, relaxation rate, and percent relaxation. Relaxation rate was strain-dependent, consistent with nonlinear superposition or Schapery models but not with quasilinear viscoelasticity (QLV). Trends in exercise data suggest that with exercise, tendons assume the elastic character of younger rats (lower elastic modulus and ultimate stress). PMID:23549897

Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

Czech Academy of Sciences Publication Activity Database

Mancini, M.; Petretto, E.; Kleinert, C.; Scavone, A.; De, T.; Cook, S.; Šilhavý, Jan; Zídek, Václav; Pravenec, Michal; d´Amati, G.; Camici, P.G.

2013-01-01

Roč. 108, č. 1 (2013), s. 316 ISSN 0300-8428 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : arterial hypertension * coronary circulation * myocardial ischemia * spontaneously hypertensive rat * recombinant inbred strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.955, year: 2013

Uptake of elemental mercury and activity of catalase in rat, hamster, guinea-pig, normal and acatalasemic mice

International Nuclear Information System (INIS)

Eide, I.; Syversen, T.L.M.

1982-01-01

Uptake of elemental mercury after inhalation (3.5 mg/m 3 ) and the activity of catalase in brain, liver, kidney and blood were investigated in rat, hamster, guinea-pig, and normal and acatalasemic mice. The uptake of mercury in the species investigated varied considerably, being highest in the two strains of mice, followed by rat and hamster, and lowest in the guinea-pig. The uptake seemed to be more dependent on pulmonary ventilation than on the activity of catalase. The two strains of mice were exposed to a wide range of mercury concentrations in air (0.002-3.5 mg/m 3 ). The content of mercury in brain, liver and kidney was linearly dependent on the mercury concentration in the air, whereas in blood this relationship was exponential. At the lower concentraions of mercury in the inhaled air, the mercury level in blood was significantly lower, and in kidney higher in the acatalasemic mice compared to the normal ones. In acatalasemic mice the mercury content in the liver has higher at all concentrations investigated, whereas in brain no difference between the two strains was found. (author)

Identification of cytochrome P450 differentiated expression related to developmental stages in bromadiolone resistance in rats (Rattus norvegicus)

DEFF Research Database (Denmark)

Markussen, Mette; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

over-express the Cyp2a1 gene. TGhe altered gene expression has been suggested to be involved in the bromadiolone resistance by facilitating enhanced anticoagulant metabolism. To investigate the gene expression of these cytochrome P450 genes in rats of different developmental stages we compared...... expression profiles, from 8-, 12- and 20-week-old resistant rats of the Danish strain to profiles of anticoagulant-susceptible rats of same ages. The three age-groups were selected to represent a group of pre-pubertal, pubertal and adult rats. We found expression profiles of the pre-pubertal and pubertal...... resistant rats to concur with profiles of the adults suggesting that cytochrome P450 enzymes are involved in the Danish bromadiolone resistance regardless of developmental stage. We also investigated the relative importance of the six cytochrome P450s in the different development stages of the resistant...

Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

DEFF Research Database (Denmark)

Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

2012-01-01

A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

Rat Models of Cardiovascular Disease Demonstrate Distinctive Pulmonary Gene Expressions for Vascular Response Genes: Impact of Ozone Exposure

Science.gov (United States)

Comparative gene expression profiling of multiple tissues from rat strains with genetic predisposition to diverse cardiovascular diseases (CVD) can help decode the transcriptional program that governs organ-specific functions. We examined expressions of CVD genes in the lungs of ...

The effect of olive-pomace oil on different blood parameters in streptozotocin induced diabetic rats

International Nuclear Information System (INIS)

Yousaf, M.J.; Naveed, A.K.; Khan, S.; Shah, S.Z.H.

2014-01-01

To determine the effects of olive-pomace oil on glycemic status and lipid profile in diabetes. Study Design: Randomized controlled trial. Place and Duration of Study: Department of Biochemistry, Army Medical College, Rawalpindi in collaboration with Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi and National Institute of Health, Islamabad from March 2010 to June 2011. Material and Methods: Seventy male albino rats of Sprague-Dawley strain were randomly divided into two groups of 35 rats each. Rats were rendered diabetic by injecting streptozotocin. Group 1 and group 2 were given normal rodent diet and olive pomace oil supplemented diet respectively for 6 weeks. At the end of the experiment fasting blood glucose and lipid profile were measured for comparison. Results: There was significant increase in high density lipoprotein and significant decrease of blood glucose, total cholesterol and low density lipoprotein of group II rats when compared with group I (control). Conclusion: Olive pomace oil can significantly improve fasting blood glucose and lipid profile in diabetic rats. (author)

Biosafety Assessment of Microbial Strains Used in Biotechnology According to Their Taxonomy

Directory of Open Access Journals (Sweden)

Natalia I. Sheina

2017-03-01

Full Text Available A great variety of biotechnological products are now widely used in different ways in agriculture, medicine, food manufacturing and other areas of our life. Industrialized societies now more than ever depend on the use of genetically engineered products, with many of them synthesized using recombinant strains of microorganisms. There is an opinion that microbial strains used in biotechnology are potentially harmful for human health and the environment. Similar to many other countries, we have enacted environmental legislation in an effort to balance the risks and benefits of using biotechnological strains. Although environmental monitoring rules focus mainly on safety assessments of chemicals, the biosafety assessment of microbial strains used in biotechnology is a very important issue as well. This article summarizes 15 years of research on the biotechnological strains of microbes widely used as producers of various biological substances for industrial purposes, and their environmental and biotechnological applications. In our survey, we tried to evaluate possible adverse effects (general toxicity and damage to the immune system, potential sensitizing effects, and damage to normal microbiota caused by these microbes. It was shown that microscopical fungi of genera Aspergillus, Penicillium and Candida, and some gram-negative bacteria can affect the immune system and disrupt the normal balance of microbial flora of the intestinal tract in rats. The actinomycetes are less dangerous in that they cause fewer side effects. The investigation data obtained can be used to develop safety and hygienic standards for industrial microbes that will help decrease or minimize the occupational risk of infection or damage to the immune system when working with biotechnological strains of microbes.

Probiotic Lactobacillus reuteri alleviates the response to gastric distension in rats.

Science.gov (United States)

Duncker, Swantje C; Kamiya, Takeshi; Wang, Lu; Yang, Pingchang; Bienenstock, John

2011-10-01

Probiotic lactic acid bacteria have been reported to alleviate symptoms in patients with irritable bowel syndrome. However, they have not been tested for use in functional gastric disease. We therefore investigated if strains previously shown to protect from response to colorectal distension (CRD) in rats also modulate response to gastric distension (GD). Healthy, male Sprague-Dawley rats were treated with viable, heat-killed, gamma-irradiated Lactobacillus reuteri or viable Lactobacillus plantarum wild type (WT), L. plantarum Dlt¯mutant, conditioned medium or medium control (9 d), and subjected to GD under anesthesia using an i.g. Teflon catheter. Effects were measured by heart rate (HR) changes during noxious distension (60 mm Hg) compared to baseline HR values. We also investigated the localization of viable, green fluorescent protein-transfected bacteria in the stomach mucosa. Viable L. reuteri decreased the bradycardia induced by noxious GD compared to placebo controls (P reuteri and conditioned medium did not have a protective effect in GD. Viable L. plantarum WT and Dlt¯mutant, previously shown to be effective antinociceptive agents in CRD, showed no protective effect in GD. All viable bacteria were associated with the pars glandularis of the rat stomach. Thus, we conclude that the antinociceptive mechanisms of action of probiotic bacteria differ between the stomach and the colon. Symptom alleviation cannot be attributed to the localization of the bacteria in the stomach. Information derived from effects of CRD cannot be extrapolated to effects in the stomach, which are likely to be strain and organ specific.

Effect of Piper betel leaf stalk extract on protein metabolism in reproductive tissues of male albino rats

OpenAIRE

V Vengaiah; A Govardhan Naik; C Changamma

2015-01-01

Objective: To know the impact of Piper betel leaf stalk (P. betel) extract on Protein and energy metabolism and its role in male albino rats. Methods: Healthy adult (3-4 months old) male Wistar strain albino rats were administered with betel leaf stalk extract, at the dose of 50 mg/kg/day through oral gavages for 15 days. Twenty four hours after the last dose, the animals were autopsied. In order to assess antifertility effect in testis, epididymis, seminal vesicle and prostate gland, esti...

Increased risk of cataract development in WNIN-obese rats due to accumulation of intralenticular sorbitol.

Science.gov (United States)

Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Balakrishna, Nagalla; Validandi, Vakdevi; Pullakhandam, Raghu; Reddy, Geereddy Bhanuprakash

2013-05-01

Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat- and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat- or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose- or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/GR-Ob rats. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Locomotion and physical development in rats treated with ionizing radiation in utero

International Nuclear Information System (INIS)

Zaman, M.S.; Hupp, E.W.; Lancaster, F.E.

1993-01-01

Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis.

Science.gov (United States)

Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

2016-01-01

Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms

The carotid body of the spontaneous insulin-dependent diabetic rat

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Clarke J.A.

1999-01-01

Full Text Available The carotid bodies from adult spontaneous insulin-dependent diabetic rats (strain BB/S were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde and compared with the organs from control rats (strain BB/Sc prepared in the same way. Serial 5-µm sections were cut, stained, and using an interactive image analysis system, were analysed to determine the volumes of the carotid body and its vascular and extravascular compartments. There was no evidence of systemic arterial disease in the carotid stem arteries in either group of animals, and the microvasculature of the organs appeared normal by light microscopy. The volume of the carotid body was unchanged 3 months after the onset of diabetes but was increased at 6 months. The total vascular volume of the organ was unchanged, but the volume of the small vessels (5-12 µm was increased. In the control group the small vessels comprised 5% of the total volume of the carotid body, or about 44% of the vascular compartment. The percentage of small vessels increased at 3 months in the diabetic group, but had returned to normal at 6 months. The extravascular volume followed the same pattern as the total carotid body volume and so did not change appreciably when expressed as a percentage of the total volume of the organ. The increase in size of the carotid body in diabetic rats is due, therefore, to an augmented extravascular volume. In one diabetic specimen the carotid sinus nerve showed signs of diabetic neuropathy, axonal swelling and intramyelinic oedema. The clinical implications of these results are discussed.

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

DEFF Research Database (Denmark)

Kelsen, Jesper; Larsen, Marianne; Sørensen, Jens Christian H.

2010-01-01

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats ...

Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

International Nuclear Information System (INIS)

Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

1988-01-01

The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted)

Measuring Regional Changes in the Diastolic Deformation of the Left Ventricle of SHR Rats Using microPET Technology and Hyperelastic Warping

International Nuclear Information System (INIS)

Gullberg, Grant T; VERESS, ALEXANDER I.; WEISS, JEFFREY A.; HUESMAN, RONALD H.; REUTTER, BRYAN W.; TAYLOR, SCOTT E.; SITEK, AREK; FENG, BING; YANG, YONGFENG; GULLBERG, GRANT T.

2008-01-01

The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping the template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R2 = 0.96), circumferential strain (R2 = 0.96), radial strain (R2 = 0.93), and longitudinal strain (R2 = 0.76) (p < 0.001 for all cases). The technology was applied to microPET image data of two spontaneously hypertensive rats (SHR) and a WKY control. Regional analysis revealed that, the lateral freewall in the SHR subjects showed the greatest deformation compared with the other wall segments. This work indicates that warping can accurately predict the strain distributions during diastole from the analysis of microPET data sets

Measuring Regional Changes in the Diastolic Deformation of the Left Ventricle of SHR Rats Using microPET Technology and Hyperelastic Warping

Energy Technology Data Exchange (ETDEWEB)

Gullberg, Grant T; VERESS , ALEXANDER I.; WEISS, JEFFREY A.; HUESMAN, RONALD H.; REUTTER, BRYAN W.; TAYLOR , SCOTT E.; SITEK , AREK; FENG, BING; YANG , YONGFENG; GULLBERG, GRANT T.

2008-04-04

The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping the template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R2 = 0.96), circumferential strain (R2 = 0.96), radial strain (R2 = 0.93), and longitudinal strain (R2 = 0.76) (p<0.001for all cases). The technology was applied to microPET image data of two spontaneously hypertensive rats (SHR) and a WKY control. Regional analysis revealed that, the lateral freewall in the SHR subjects showed the greatest deformation compared with the other wall segments. This work indicates that warping can accurately predict the strain distributions during diastole from the analysis of microPET data sets.

Eccentric contractions affect muscle membrane phospholipid fatty acid composition in rats

DEFF Research Database (Denmark)

Helge, Jørn Wulff; Therkildsen, K J; Jørgensen, T B

2001-01-01

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised...... muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 +/- 0.6; 16.4 +/- 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 +/- 0.1 and 2.7 +/- 0.......1% of total fatty acids, respectively) was uniformly higher across groups (P fatty acids) compared to the control leg (38.2 +/- 0...

A new zearalenone biodegradation strategy using non-pathogenic Rhodococcus pyridinivorans K408 strain.

Science.gov (United States)

Kriszt, Rókus; Krifaton, Csilla; Szoboszlay, Sándor; Cserháti, Mátyás; Kriszt, Balázs; Kukolya, József; Czéh, Arpád; Fehér-Tóth, Szilvia; Török, Lívia; Szőke, Zsuzsanna; Kovács, Krisztina J; Barna, Teréz; Ferenczi, Szilamér

2012-01-01

Zearalenone (hereafter referred to as ZEA) is a nonsteroidal estrogenic mycotoxin produced by several Fusarium spp. on cereal grains. ZEA is one of the most hazardous natural endocrine disrupting chemicals (EDC) which induces hyper estrogenic responses in mammals. This can result in reproductive disorders in farm animals as well as in humans. Consequently, detoxification strategies for contaminated crops are crucial for food safety. In this study we have developed a bacterial based detoxification system using a non-pathogen Rhodococcus pyridinivorans K408 strain. Following 5 days treatment of ZEA with R. pyridinivorans K408 strain HPLC analyses showed an 87.21% ZEA-degradation efficiency of the bacterial enzyme systems. In another approach, the strain biotransformation ability has also been confirmed by a bioluminescent version of the yeast estrogen screening system (BLYES), which detected an 81.75% of biodegradability of ZEA, in a good agreement with the chemical analyses. Furthermore, the capacity of R. pyridinivorans to eliminate the estrogenic effects of ZEA was tested by using an immature uterotrophic assay. Prepubertal female rats were treated with vehicle (olive oil), 17β-estradiol, ZEA (0.1-1-5-10 mg/kg body weight) and LB broth containing 500 mg/l ZEA that has already been incubated with or without Rhodococcus pyridinivorans K408 strain. Uterine weights were measured and the mRNA level changes relating to apelin, aquaporin 5, complement component 2, and calbindin-3 genes were measured by qRT-PCR. These genes represent the major pathways that are affected by estromimetic compounds. Zearalenone feeding significantly increased the uterus weight in a dose dependent manner and at the same time upregulated complement component 2 and calbindin-3 expression as well as decreased apelin and aquaporin 5 mRNA levels comparable to that seen in 17β-estradiol exposed rats. In contrast, LB broth in which ZEA was incubated with Rhodococcus pyridinivorans K408 prior to

A new zearalenone biodegradation strategy using non-pathogenic Rhodococcus pyridinivorans K408 strain.

Directory of Open Access Journals (Sweden)

Rókus Kriszt

Full Text Available Zearalenone (hereafter referred to as ZEA is a nonsteroidal estrogenic mycotoxin produced by several Fusarium spp. on cereal grains. ZEA is one of the most hazardous natural endocrine disrupting chemicals (EDC which induces hyper estrogenic responses in mammals. This can result in reproductive disorders in farm animals as well as in humans. Consequently, detoxification strategies for contaminated crops are crucial for food safety. In this study we have developed a bacterial based detoxification system using a non-pathogen Rhodococcus pyridinivorans K408 strain. Following 5 days treatment of ZEA with R. pyridinivorans K408 strain HPLC analyses showed an 87.21% ZEA-degradation efficiency of the bacterial enzyme systems. In another approach, the strain biotransformation ability has also been confirmed by a bioluminescent version of the yeast estrogen screening system (BLYES, which detected an 81.75% of biodegradability of ZEA, in a good agreement with the chemical analyses. Furthermore, the capacity of R. pyridinivorans to eliminate the estrogenic effects of ZEA was tested by using an immature uterotrophic assay. Prepubertal female rats were treated with vehicle (olive oil, 17β-estradiol, ZEA (0.1-1-5-10 mg/kg body weight and LB broth containing 500 mg/l ZEA that has already been incubated with or without Rhodococcus pyridinivorans K408 strain. Uterine weights were measured and the mRNA level changes relating to apelin, aquaporin 5, complement component 2, and calbindin-3 genes were measured by qRT-PCR. These genes represent the major pathways that are affected by estromimetic compounds. Zearalenone feeding significantly increased the uterus weight in a dose dependent manner and at the same time upregulated complement component 2 and calbindin-3 expression as well as decreased apelin and aquaporin 5 mRNA levels comparable to that seen in 17β-estradiol exposed rats. In contrast, LB broth in which ZEA was incubated with Rhodococcus pyridinivorans K

Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats.

Science.gov (United States)

Al-Numair, Khalid S; Chandramohan, Govindasamy; Veeramani, Chinnadurai; Alsaif, Mohammed A

2015-09-01

The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats. The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal. The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.

Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

Science.gov (United States)

Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

2012-01-01

Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

Science.gov (United States)

Vinod, K Yaragudri; Xie, Shan; Psychoyos, Delphine; Hungund, Basalingappa L; Cooper, Thomas B; Tejani-Butt, Shanaz M

2012-01-01

While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

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K Yaragudri Vinod

Full Text Available BACKGROUND: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. METHODOLOGY/PRINCIPAL FINDINGS: The role of the endocannabinoid (eCB system in depressive behavior was examined in Wistar Kyoto (WKY rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD. Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. CONCLUSIONS/SIGNIFICANCE: These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

Sleep deprivation and spike-wave discharges in epileptic rats

OpenAIRE

Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Vossen, J.M.H.; Luijtelaar, E.L.J.M. van

1995-01-01

The effects of sleep deprivation were studied on the occurrence of spike-wave discharges in the electroencephalogram of rats of the epileptic WAG/Rij strain, a model for absence epilepsy. This was done before, during and after a period of 12 hours of near total sleep deprivation. A substantial increase in the number of spike-wave discharges was found during the first 4 hours of the deprivation period, whereas in the following deprivation hours epileptic activity returned to baseline values. I...

Screening and characterization of purine nucleoside degrading lactic acid bacteria isolated from Chinese sauerkraut and evaluation of the serum uric acid lowering effect in hyperuricemic rats.

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Ming Li

Full Text Available Hyperuricemia is well known as the cause of gout. In recent years, it has also been recognized as a risk factor for arteriosclerosis, cerebrovascular and cardiovascular diseases, and nephropathy in diabetic patients. Foods high in purine compounds are more potent in exacerbating hyperuricemia. Therefore, the development of probiotics that efficiently degrade purine compounds is a promising potential therapy for the prevention of hyperuricemia. In this study, fifty-five lactic acid bacteria isolated from Chinese sauerkraut were evaluated for the ability to degrade inosine and guanosine, the two key intermediates in purine metabolism. After a preliminary screening based on HPLC, three candidate strains with the highest nucleoside degrading rates were selected for further characterization. The tested biological characteristics of candidate strains included acid tolerance, bile tolerance, anti-pathogenic bacteria activity, cell adhesion ability, resistance to antibiotics and the ability to produce hydrogen peroxide. Among the selected strains, DM9218 showed the best probiotic potential compared with other strains despite its poor bile resistance. Analysis of 16S rRNA sequences showed that DM9218 has the highest similarity (99% to Lactobacillus plantarum WCFS1. The acclimated strain DM9218-A showed better resistance to 0.3% bile salt, and its survival in gastrointestinal tract of rats was proven by PCR-DGGE. Furthermore, the effects of DM9218-A in a hyperuricemia rat model were evaluated. The level of serum uric acid in hyperuricemic rat can be efficiently reduced by the intragastric administration of DM9218-A (P<0.05. The preventive treatment of DM9218-A caused a greater reduction in serum uric acid concentration in hyperuricemic rats than the later treatment (P<0.05. Our results suggest that DM9218-A may be a promising candidate as an adjunctive treatment in patients with hyperuricemia during the onset period of disease. DM9218-A also has potential

Mechanisms Of Co-Morbidities Associated With The Metabolic Syndrome: Insights From The JCR:La-Cp Corpulent Rat Strain