Increasing peak bone mass at skeletal maturity, minimizing bone loss during middle age and after menopause, and increasing bone mass and preventing falls in advanced age are important measures for preventing osteoporotic fractures in women. Exercise has generally been considered to have a positive influence on bone health. This paper reviews the effects of treadmill exercise on bone in young, adult, ovariectomized, and osteopenic female rats. Treadmill exercise increases cortical and cancellous bone mass of the tibia as a result of increased bone formation and decreased bone resorption in young and adult rats. The increase in lumbar bone mass seems to be more significant when long-term exercise is applied. Treadmill exercise prevents cancellous bone loss at the tibia as a result of suppressed bone resorption in ovariectomized rats, and increases bone mass of the tibia and mechanical strength of the femur, as a result of suppressed bone resorption and increased bone formation in osteopenic rats after ovariectomy. Treadmill exercise transiently decreases the serum calcium level as a result of accumulation of calcium in bone, resulting in an increase in serum 1,25-dihydroxyvitamin D3 level and a decrease in serum parathyroid hormone level. We conclude that treadmill exercise may be useful to increase bone mass in young and adult rats, prevent bone loss in ovariectomized rats, and increase bone mass and bone strength in osteopenic rats, especially in the long bones at weight-bearing sites. Treadmill exercise may have a positive effect on the skeleton in young, and adult, ovariectomized, and osteopenic female rats.
The blue-breasted quail (Coturnix chinensis), the smallest species in the order Galliforms, is a candidate model animal for avian developmental engineering because it is precocious and prolific. This species requires 17 days to hatch and 8 to 9 weeks to mature to an adult body weight of about 50 g, whereas the Japanese quail (Coturnix japonica) requires 16 days to hatch and 6 to 8 weeks to mature to an adult body weight of 100 to 150 g. The early embryo is the most challenging embryonic stage in terms of culture and manipulation for avian biotechnology. We have evaluated various conditions for the culture of blue-breasted quail embryos from the blastoderm stage to hatching. A hatchability rate of 26% (10/39) is among the best of the various culture conditions examined in the present study and the embryo culture system should facilitate advances in avian biotechnology.
An fa allele of the leptin receptor gene (Leprfa) of the Zucker fatty rat was introduced into the genome of the Spontaneously Diabetic Torii (SDT) rat, an inbred model of nonobese type 2 diabetes mellitus, through the `Speed congenic method'. The newly established congenic strain of a SDT rat for Leprfa was maintained by intercrossing between fa-heterozygous littermates, and the phenotypes related to obesity and diabetes were investigated till 32 wks of age. SDT fa/fa rats of both sexes exhibited obesity, adiposity and insulin resistance associated with hyperphagia from the loss of leptin action. Interestingly, they developed diabetes from 5 wks of age in males and 8 wks in females with the incidences reaching 100% at 16 wks in males and 73% at 32 wks in females. In contrast, heterozygous (+/fa) and wild-type (+/+) rats developed spontaneous nonobese diabetes in males from approximately 20 wks, but not in females, as with the original SDT rats. These results indicate that the fa gene accelerates the onset of diabetes in SDT rats by making adiposity and/or insulin resistance as potent risk factors for development of their diabetes. The SDT.Leprfa congenic rat strain is expected to be a novel model of obesity-related diabetes and could be a useful tool for studies of the genetic backgrounds of diabetes in response to fa-induced obesity.
Although galanin (GAL) protects hippocampal neurons from ischemic damage, no study has examined ischemia-related changes in endogenous GAL in the hippocampal dentate gyrus. We investigated the chronological changes of GAL, well-known as the potassium channel opener, expression in the dentate gyrus at various times after 5 min of transient forebrain ischemia in gerbils. A few GAL-immunoreactive (IR) neurons were found in the polymorphic layer of the sham-operated group. Three hours after ischemia-reperfusion, the pattern of GAL immunoreactivity was similar to that of the sham-operated group and the number of GAL-IR neurons and immunoreactivity were highest 12 h after ischemic insult. At this time, GAL-IR neurons in the polymorphic layer showed strong GAL immunoreactivity. Thereafter, GAL-IR neurons and immunoreactivity significantly decreased in the dentate hilar region. Four days after ischemic insult, GAL-IR neurons were not detectable. In addition, the results of a Western blot study showed a pattern of GAL expression similar to the immunohistochemical changes. GAL protein content also was highest 12 h after ischemia. In conclusion, the increased expression of endogenous GAL in the dentate gyrus after ischemia is related to response to the ischemic damage.
The Ca2+ channel α1B subunit is a pore-forming component capable of generating N-type Ca2+ channel activity. Although the N-type Ca2+ channel plays a role in a variety of neuronal functions, α1B-deficient mice with a CBA/JN genetic background show no apparent behavioral or anatomical-histological abnormality, presumably owing to compensation by other Ca2+ channels. In this study, we examined the mRNA expression of the α1A, α1C, α1D, α1E, β1, β2, β3 and β4 subunits in the olfactory bulb, cerebral cortex, hippocampus and cerebellum of α1B-deficient mice. We found that the mRNA expression levels of the α1A, α1C, α1D, α1E, β1, β2, β3 and β4 subunits were the same in the olfactory bulbs of wild, heterozygous and homozygous α1B-deficient mice. In the cerebral cortex, α1A mRNA in homozygous α1B-deficient mice was expressed at a higher level than in wild or heterozygous mice, but no difference in the expression levels of the α1C, α1D, α1E, β1, β2, β3 and β4 subunits was found among wild, heterozygous and homozygous mice. In hippocampus and cerebellum, β4 mRNA in homozygous α1B-deficient mice was expressed at a higher level than in wild or heterozygous mice, but no difference in the expression levels of the α1A, α1C, α1D, α1E, β1, β2 and β3 subunits was found among wild, heterozygous and homozygous mice. These results suggest that the compensatory mechanisms differ in different brain regions of α1B-deficient mice with a CBA/JN genetic background.
InnoPol®, a poly(D,L-lactic-co-glycolic acid) [PLGA] 65/35 scaffold manufactured by special gas foaming methods in Korea, was subjected to tests to evaluate the degradation and tissue compatibility characteristics and long-term systemic toxicity in mice and rats. C57BL/6 mice and SD rats were implanted subcutaneously with 3-mm- and 1-mm-thick InnoPol® circular discs, 10 mm in diameter, respectively, and sacrificed 8, 12, and 24 weeks after implantation. No test material-related effects were observed in mortality, clinical signs, body weight gain, food and water consumption, ophthalmologic signs, urinalysis, hematology, serum biochemistry parameters and organ weights of all animals implanted with InnoPol®. Also, there were no systemic symptoms including metabolic alterations and inflammatory reactions in either mice or rats. In addition, no gross pathological findings, except skin lesions around the implantation sites, were found in the major organs. Although mild inflammation at the site of InnoPol® implantation was confirmed from hematoxylin and eosin or Masson's trichrome staining at 8-12 weeks, the reactions had disappeared at 24 weeks following complete degradation of the scaffold, leaving granulomatous tissues that were similar to surgical wounds in sham operation controls without implants. These results suggest that InnoPol® possesses good mechanical properties and tissue compatibility and does not cause any systemic toxicity other than transient local inflammatory reactions at the implantation site, and that it might be useful in applications as a medical device for implantation.
The SAMP1/Sku mouse is a substrain of the SAMP1 (senescence-accelerated-mouse prone 1) which exhibits renal mononuclear cell infiltration from a younger age. We hypothesized that this renal characteristic is related to the incidence of tubulointerstitial nephritis (TIN). The purpose of the present study was to evaluate the applicability of the SAMP1/Sku mouse as a murine model for TIN. TIN was experimentally induced by unilateral ureteral obstruction (UUO). The SAMP1/Sku and control ICR of both sexes received either a sham or UUO operation and were sacrificed 7 days after the operation. The kidneys of the mice were observed histopathologically, immunohistochemically and semiquantitatively. UUO kidneys showed mononuclear cell infiltration, tubular atrophy and interstitial fibrosis. In males, semiquantitative scores of mononuclear cell infiltration, tubular atrophy, and F4/80, α-smooth muscle actin (α-SMA) and transforming growth factor (TGF)-β1 reactions were significantly higher in SAMP1/Sku than in ICR. Likewise, in females, tubular atrophy and F4/80 reaction scores were significantly higher in SAMP1/Sku than in ICR. In conclusion, induction of TIN damage by UUO was more serious in SAMP1/Sku mice than in ICR. Therefore, we propose that SAMP1/Sku mice, especially male SAMP1/Sku, have congenital risk factors for the development of TIN.
The aim of this study was to examine the changes in autonomic control of the heart associated with classical appetitive conditioning in rats. We trained rats to learn that a movement into a test chamber was followed by delivery of reward (contextual conditioning) and performed power spectral analysis of heart rate variability from electrocardiograms recorded using the telemetry system. We investigated the sympathovagal balance of autonomic regulation of the heart in response to not only the conditioned stimulus (the movement into the test chamber), but also the unconditioned stimulus (reward), and compared the results of these two kinds of emotional states; it might be considered that "the reward-expecting state" is evoked by the conditioned stimulus and "the reward-receiving state" is evoked by the unconditioned stimulus in rats. The reward-expecting state resulted in a significant increase in both low frequency (LF) power and high frequency (HF) power with no change in heart rate (HR) and LF/HF ratio, indicating that both sympathetic and parasympathetic activity increased with no change in sympathovagal balance. The reward-receiving state resulted in a significant increase in HR and a significant decrease in LF power, HF power, and LF/HF ratio, indicating that both sympathetic and parasympathetic activity decreased with predominance in the parasympathetic activity. These results suggest that the method performed in our present study might be useful for distinguishing between two different emotional states evoked by classical appetitive conditioning in rats.
The TSOD mouse has been established as an inbred strain with spontaneous development of diabetes mellitus as the first clinical signs of diabetes. Polydipsia and polyuria are observed at about 2 months old only in male mice, after which hyperglycemia and hyperinsulinemia are detected. Following these symptoms obesity gradually develops until about 12 months old. In histopathological examination of the pancreas, severe hypertrophy of pancreatic islets was observed due to proliferation and swelling of B cells. In the kidney, thickening of the basement membrane in glomeruli and an increase of the mesangial area were observed at 18 months old. Motor neuropathy in TSOD mice began to appear at 14 months old and most male mice at 17 months old showed weakness of front and hind paws caused by neuron degeneration in the peripheral nerve. In sensory neuropathy, the threshold in the tail pressure test decreased significantly at 12 months old. Light microscopic and electron microscopic examination of sciatic nerves showed a decrease in the density of nerve fibers by the endoneural fibrosis and loss of these fibers. Degenerative changes of myelinated fibers, separation of myelin sheaths with intralamellar edema and remyelination were frequently observed. In the severely affected nerve fibers, the lamellar structure was completely destroyed and macrophages migrated around the myelin sheath or invaded the intramyelin space. Considering these findings similar to non-insulin dependent diabetes mellitus (NIDDM) in humans, the TSOD mouse should be a useful model for the pathogenic study of diabetic complications, especially of peripheral neuropathy.
The present study contains information about proper microbiological monitoring of laboratory animals' health and the standardization of microbiological monitoring methods in Korea. Microbiological quality control for laboratory animals, composed of biosecurity and health surveillance, is essential to guard against research complications and public health dangers that have been associated with adventitious infections. In this study, one hundred and twenty-two mice and ninety rats from laboratory animal breeding companies and one animal facility of the national universities in Korea were monitored in 2000-2003. Histopathologically, thickening of the alveolar walls and lymphocytic infiltration around the bronchioles were observed in mice and rats from microbiologically contaminated facilities. Cryptosporidial oocysts were observed in the gastric pits of only conventionally-housed mice and rats. Helicobacter spp. infection was also detected in 1 of 24 feces DNA samples in mice and 9 of 40 feces DNA samples in rats by PCR in 2003, but they were not Helicobacter hepaticus. This paper describes bacteriological, parasitological, and virological examinations of the animals.
While the normal estrous cycle of adequately acclimated female rats was replaced by a persistent estrus (PE) under continuous lighting, the onset of PE was delayed following several irregular cycles without acclimation or after acclimation for one week, suggesting that transportation induces a significant critical stress.
The optimum dose for establishing superovulation in mice of Fertirelin Acetate (FA), an LH-RH analogue, was examined. Mice were subcutaneously injected with 5 IU of hCG at 17:00 (Day 0), and with various doses of FA (0.001 to 1.0 μg) five times at 4 h intervals on and after 22:00 on Day 0. To induce ovulation, 5 IU of hCG was again injected subcutaneously at 17:00 on Day 2. In the groups administered with doses ranging from 0.01 to 0.5 μg of FA, the number of ovulated eggs was significantly (p<0.05) larger than in the control group (12.9 ± 5.9). The greatest number of ovulated eggs (22.6 ± 7.3) was obtained in the group administered with 0.025 μg of FA. The results indicate that the effective dose of LH-RH analogue, FA, is between 0.1 and 0.5 μg for superovulation induction in mice.
A case of spontaneous malignant lymphoma in a Japanese macaque (Macaca fuscata) was pathologically, etiologically and virologically studied. Nasal cavity was involved in the neoplastic lesions in addition to lymphoid and visceral tissues. Histopathological analyses revealed the presence of neoplastic cells classified into histiocytic Hodgkin-like cells and Reed-Sternberg-like cells. Histiocytic Hodgkin-like cells were CD16+ and CD20+, and the CD16+ cells were also positive for simian Epstein-Barr virus (sEBV)-encoded early RNA transcripts. RS-like cells were negative for CD3, CD16 and CD20. Antibodies to early antigen of sEBV were detected, while antibodies to simian T-cell leukemia virus-1 were negative. The case may correspond to EBV-associated nasal type NK/T-cell lymphoma in humans rather than Hodgkin lymphoma.
Hyperplastic cells in subcapsular cell hyperplasia (SCH) lesion in adrenal glands of female IQI/Jic mice were examined by electron microscopy. These cells were small and polygonal, and had irregular nuclei, elongated mitochondria with lamellar cristae and dense lipid droplets. While these cells showed different features, some of them had desmosomes and basement membranes, and a few round mitochondria with tubular cristae as endocrine cells. These findings suggest that hyperplastic cells in SCH lesions might originate from endocrine blastemic cells.