Placentas from spontaneously hypertensive rats and control strain Wistar-Kyoto rats

Placentas from spontaneously hypertensive rats (SHR) were compared to those of control strain Wistar-Kyoto rats (WKY) at 15, 18 and 20 days of gestation using light microscopic techniques. Placental lesions similar to those in pregnant hypertensive women were absent in both strains; however, other abnormalities were noted. Hemorrhage at the lateral edges of the decidua basalis appeared to be more extensive in the SHR than WKY at 15 days. At the same time, bloody vaginal discharges were noted in 18% of the SHR. Leukocytic encapsulation of 20-day placentas with viable fetuses was noted in two SHR dams but not in any WKY. It is thought that these differences may be related to the high maternal blood pressure in the SHR or to hormonal imbalance associated with the stress response in the SHR due to frequent monitoring of blood pressure.     

Nephrotoxicity of cyclosporin A in diabetic breeding rats breeding rats

A considerable number of studies were carried out on patients receiving Cyclosporin A (CSA) after bone marrow, heart and kidney transplants. More recently this drug has been used as an immunosuppressive agent in the management of type 1 diabetes. Moreover the increase of creatinine levels in CSA-treated patients and animals has led the researchers to believe that this drug may be responsible for irreversible nephrotubular side effects.Our aim was, therefore, to study the hispathological effects of CSA on kidneys of bio breeding (BB) rats, which develop diabetes spontaneously.Animals were treated for 30 and 60 days with daily injections of 8 mg/kg body wt of CSA, dissolved in 2 ml of Intralipid 10% (Pierrel), given intraperitoneally (control animals received only Intralipid). At the end of the experiments animals were sacrificed under ether anaesthesia and the kidneys removed and processed for light microscopy, using standard procedures. After a 30-day administration of CSA, the tubular and glomerular structures appeared unchanged or, in some cases, only a few cells, in the proximal tubules, showed slight vacuolation. After 60 days of CSA administration, the elements of the proximal profiles showed a considerable degree of cytoplasmic vacuolation. These vacuoles resulted positive to PFABB, Sudan Black B, PAS and alkaline tetrazolium reactions. Distal tubular profiles, loops of Henle and glomeruli were unaffected.Our morphological findings demonstrate that CSA causes nephrotubular modifications, when administered in therapeutic doses of only 10 mg/kg body wt, as in many clinical schedules. Moreover data could be consistent with a possible reversion to the normal structural appearance.     

Genetics of obesity of Zucker rats and Koletsky rats.

The breeding data on Zucker rats and on Koletsky rats confirm that the obesity in these two strains of rats is inherited recessively and results from single gene mutations. Mating a Zucker heterozygote to a Koletsky heterozygote produced obese F1 progeny. Inter-stock breeding results indicate that the obesity in the Zucker-Koletsky hybrid stock is also inherited in a recessive manner. The gene that controls obesity in the Zucker rats, fatty (fa), and the gene that controls obesity in the Koletsky rats, f, are thus alleles at the same locus. We propose that f be renamed fak until it can be proven that fa and fak are identical.     

Beyond knockout rats

The ability to “knockout” specific genes in mice via embryonic stem (ES) cell-based gene-targeting technology has significantly enriched our understanding of gene function in normal and disease phenotypes. Improvements on this original strategy have been developed to enable the manipulation of genomes in a more sophisticated fashion with unprecedented precision. The rat is the model of choice in many areas of scientific investigation despite the lack of rat genetic toolboxes. Most Recent advances of zinc finger nucleases (ZFNs) and rat ES cells are diminishing the gap between rat and mouse with respect to reverse genetic approaches. Importantly, the establishment of rat ES cell-based gene targeting technology, in combination with the unique advantages of using rats, provides new, exciting opportunities to create animal models that mimic human diseases more faithfully. We hereby report our recent results concerning finer genetic modifications in the rat, and propose their potential applications in addressing biological questions.     

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60?mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10?mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65?days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15?days) but also in the long term (45?days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.     

Beyond knockout rats: New insights into finer genome manipulation in rats

The ability to “knockout” specific genes in mice via embryonic stem (ES) cell-based gene-targeting technology has significantly enriched our understanding of gene function in normal and disease phenotypes. Improvements on this original strategy have been developed to enable the manipulation of genomes in a more sophisticated fashion with unprecedented precision. The rat is the model of choice in many areas of scientific investigation despite the lack of rat genetic toolboxes. Most recent advances of zinc finger nucleases (ZFNs) and rat ES cells are diminishing the gap between rat and mouse with respect to reverse genetic approaches. Importantly, the establishment of rat ES cell-based gene targeting technology, in combination with the unique advantages of using rats, provides new, exciting opportunities to create animal models that mimic human diseases more faithfully. We hereby report our recent results concerning finer genetic modifications in the rat, and propose their potential applications in addressing biological questions.Key words: genetic manipulation, gene targeting, conditional knockout, transgenic animal, rat model, p53 knockout rat, embryonic stem cells     

Gustatory contrast in rats

Six groups of rats were presented with alternating 45-sec accessperiods to two tubes containing sucrose solutions. On some daysone group experienced a disparity in solution concentration(16% vs. 2%, 16% vs. 4%, 16% vs. 8%, and 16% vs. 12%) and onother days received the same concentration solution in bothtubes (16%, 12%, 8%, 4%, or 2%). Each of the remaining fivegroups received only one concentration solution in both tubesthroughout the experiment (16%, 12%, 8%, 4%, or 2%). Lick ratesto the different concentration solutions obtained under comparisonconditions were found to be exaggerated relative to those obtainedunder non-comparison conditions (contrast). Regression analysesperformed on the log lick ratios to the various concentrationsplotted as a function of the log ratios of the concentrationsavailable, revealed a good fit to a power function with an exponent(slope) within the range of those found in human judgments ofrelative sweetness. The slopes obtained from the regressionanalyses were a) steeper under comparison than under non-comparisoncondition and b) increased as number of within-session comparisonsincreased. The results are discussed in terms of a sensoryperceptualinterpretation of contrast effects.     

Nicotine dependence in rats

Health hazards associated with nicotine and tobacco use are well known. A contributing factor, the dependence producing potential of this drug, has become widely accepted. However, there are only a few human and animal studies that provide objective measures of the behavioral consequences of nicotine abstinence. The purpose of the present experiment was to use sensitive measures to examine behavioral disruptions that resulted when nicotine administration was terminated. Six rats were administered 96 daily intravenous infusions of nicotine (0.125 mg/kg/infusion) for at least 10 days. They were trained to respond on a tongue-operated solenoid-driven drinking device that delivered 0.005 ml of a glucose and saccharin solution (G + S) per lick. When nicotine access was terminated for six days, there was a marked suppression in behavior reinforced by the sweetened solution, and this disruption was immediately reversed when nicotine was reinstated. In contrast, nicotine removal also resulted in a decrease in food intake on the first day, but on subsequent days food intake was significantly higher than when nicotine was administered. When cotinine (0.25 mg/kg/infusion), a metabolite of nicotine was substituted for nicotine for six days, similar disruptions resulted in responding maintained by G + S, but food intake was not significantly decreased on the first day of nicotine abstinence. These findings illustrate the utility of sensitive behavioral tests to reveal effects of nicotine abstinence.