Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.
The majority of newly acquired nonhuman primates encounter serious problems adapting themselves to new environments or facilities. In particular, loss of appetite and abnormal behavior can occur in response to environmental stresses. These adaptation abnormalities can ultimately have an affect on the animal's growth and well-being. In this study, we evaluated the affects of a puzzle feeder on the food intake and abnormal behavior of newly acquired rhesus monkeys for a short period. The puzzle feeder was applied to 47- to 58-month-old animals that had never previously encountered one. We found that there was no difference in the change of food intake between the bucket condition and the puzzle feeder condition. In contrast, the time spent for consumption of food was three times longer in the puzzle feeder condition than in the bucket condition. Two monkeys initially exhibited stereotypic behavior. One showed a decreasing, and the other an increasing pattern of abnormal behavior after introduction of the puzzle feeder. In conclusion, this result suggests that over a short period, the puzzle feeder can only affect the time for food consumption since it failed to affect the food intake and did not consistently influence stereotypic behaviors in newly acquired rhesus monkeys.
Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.
Two species of the genus Phodopus, Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii), differ in their behavior. The Roborovskii hamster has high locomotor activity (hyperactivity) compared to the Djungarian hamster. In this study, we compared locomotor activity of the hamsters in different environments, and compared their brain monoamine and metabolite levels to identify the mechanism by which both hamsters move differently. Activity of Roborovskii hamsters was significantly higher than Djungarian hamsters in the open field, while no difference was observed in their home cage. Dopamine (DA) and serotonin (5-HT) levels in the whole brain of Roborovskii hamster were significantly lower and their metabolic turnover rates were significantly higher than those of the Djungarian hamster. We conclude that the difference in activity under the novel environment between both species is partly, but not entirely, explained by the difference in monoamine levels and their metabolism in the brain.
Twenty eight female Wistar rats weighing 150-200 g were used in this study and these animals were divided into 4 groups, each comprising 7 rats. The first group served as the control group, and groups 2, 3, and 4 were administered a single dose of 250 mg/kg.bw propolis, a single dose of 125 mg/kg.bw (1/2LD50) cypermethrin, and a single dose of 125 mg/kg.bw cypermethrin followed by a single dose of 250 mg/kg.bw propolis 30 min later, per os using a catheter, respectively. Twenty-four hours after propolis administration, blood and tissue (liver, kidney, and brain) samples were collected. Serum glucose, triglyceride, uric acid, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities/levels, plasma and tissue malondialdehyde (MDA) levels, and erythrocyte and tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined. Compared to group 1, significant increases in plasma and tissue MDA levels and kidney GSH-Px activity, and significant decreases in erythrocyte SOD and CAT, liver SOD and GSH-Px, kidney SOD and brain SOD, CAT and GSH-Px activities were determined in group 3. Compared to group 1, a significant increase in glucose and a significant decrease in triglyceride levels were determined in group 3. Values pertaining to group 4 were demonstrated to be closer to those of group 1.
Adiponectin, which is expressed exclusively in adipose tissue, has been shown to increase fatty acid oxidation via activation of AMP-activated kinase (AMPK) and phosphorylation of acetyl CoA carboxylase (ACC). ACC phosphorylation and carnitine palmitoyl-transferase-1 (CPT1) activity have been shown to be rate controlling factors in fatty acid oxidation. In high fat diet (HFD)-induced obese mice, we analyzed the time-course of changes in the expression of adiponectin and lipid oxidative enzymes induced by treatment with bisphenol A diglycidyl ether (BADGE) or caffeine for 8 weeks, and investigated whether the changes of adiponectin and lipid oxidative enzymes expression correlated with reduced adiposity or steatosis after 8 weeks of treatment. After 8 weeks of treatment, BADGE and caffeine had reduced body weight and epididymal adipose tissue weight in mice fed HFD, and markedly reduced the number of fatty droplets in the liver. Interestingly, the expression of adiponectin and lipid oxidative enzymes significantly increased after 2 weeks of treatment. These results indicate that the expression of adiponectin and lipid oxidative enzymes in the early stages of BADGE or caffeine treatment correlated well with the long-term anti-obesity effects.
Severely immunocompromised NOD/Shi-scid IL2Rg null (NOG) mice, which show higher engraftment efficiency, are useful as recipients in xenotransplantation studies. We generated a NOG-enhanced green fluorescent protein (EGFP) transgenic (Tg) mouse (NOG-EGFP) that was introduced the EGFP transgene from the C57BL/6-EGFP Tg mouse using the speed congenic method with a marker-assisted selection protocol (MASP). With this method, the selection of the male with the closest NOG strain type was repeated four times. When human cord blood CD34+ cells were transplanted into NOD/Shi-scid, NOG, and NOG-EGFP mice (N6), the engraftment efficiency of the NOG-EGFP mice was significantly higher than that of the NOD/Shi- scid mice and was similar to that of the NOG mice. These results suggest that the NOG-EGFP mice, which were generated using the congenic method with MASP, acquired the immunological properties of the NOG mice.
Clinically healthy rabbits were inoculated with rabbit hemorrhagic disease virus (RHDV) and the kinetics of their serum lipid parameters and liver enzymes were monitored. After RHDV inoculation, hyperlipidemia was observed (Ptriglyceride<0.0001, Pcholesterol=0.0003) along with significant increases in serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P<0.0001). An exponential increase in serum triglyceride was also seen. Thus, the presence of hyperlipidemia (from 30 h post-inoculation) in the infected rabbits points to impairment in lipid metabolism. This is the first demonstration that RHDV infection leads to hyperlipidemia, probably due to the disorder of liver enzymes associated with lipid metabolism.
In this study, in order to clarify the kinetics of leptin, we focused on the ratio of leptin concentrations in cerebrospinal fluid and serum in aged male rats, and examined the weight of epididymal fat, and the passage rate of leptin through the blood-brain barrier. In the lighter animals, the epididymal fat weight was low, while leptin concentrations in the serum and cerebrospinal fluid were also low. Conversely, in the heavier animals, the weight of epididymal fat and leptin concentrations in the serum and cerebrospinal fluid were higher. With regard to the ratio of leptin in the cerebrospinal fluid and serum, the passage rate of leptin through the blood-brain barrier was lower in the heavier animals than in the lighter animals.
The difference between genders in the composition of mouse fecal flora was examined. A polymerase chain reaction followed by denaturing gradient gel electrophoresis (DGGE) were performed on the V6-V8 regions of bacterial 16S rDNA obtained from fecal samples at 0, 1, 2, 3, 4, and 8 weeks after the introduction of mice into the laboratory from a mouse farm. Cluster analysis and non-metric multidimensional scaling (NMDS) were then performed. Male and female mice were distributed on opposite sides of the origin of the plane in NMDS at weeks 0, 2, 3, and 8. These results suggest a gender difference in the composition of intestinal flora in mice.