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Although Hatano high-avoidance and low-avoidance rats (HAA and LAA, respectively) have been selectively bred for good versus poor avoidance learning, HAA rats are known to be more reactive to stress than LAA rats. In this study, HAA and LAA female rats were compared during reproductive aging by observing estrous cycles from 8 to 11 months of age. Furthermore, these rats were allowed to live out their natural lifespans, that is, until 24 months of age, in order to compare their survival and to clarify the relationship between reproductive aging and tumor development. At eight months of age, 2 of 35 HAA rats and 20 of 35 LAA rats had abnormal estrous cycles. The median lifespan of the HAA rats (673 days) was shorter than that of the LAA rats (733 days). The incidence of pituitary neoplasia was higher in the HAA rats than in the LAA rats. These results suggest that HAA female rats (i.e., stress-reactive rats) have a shorter lifespan than LAA female rats (i.e., stress-nonreactive rats) and develop pituitary neoplasia, which was one of the causal factors in their accelerated mortality. However, the onset of an age-matched abnormal cycle did not correspond with their lifespan.
Although Slc:Wistar rats are used widely in biomedical research as outbred rats, close similarities in growth curves, survival rates, and immunological and biochemical phenotypes have been reported between Slc:Wistar and F344 inbred rats. We reported previously that nine genetic variations that were fixed in Slc:Wistar rats had identical genotypes in F344 rats. Here, we examined the genetic characteristics of Slc:Wistar rats using 27 simple-sequence length polymorphism (SSLP) markers and compared them with other Wistar stocks available in Japan and with some F344 strains. Among 27 SSLP loci, 23 (85%) were fixed in the Slc:Wistar rats, which was the highest among the other Wistar stocks. The 23 fixed loci shared identical genotypes with corresponding loci in F344 rats. Further, the predominant allele types in the unfixed loci had allele frequencies as high as 80%, and these alleles were identical in the F344 rats. When the nine genetic variations reported previously are added, a total of 32 (89%) out of the 36 loci examined were fixed and identical in the Slc:Wistar and F344 rat genomes. These findings indicate the low genetic variation in Slc:Wistar rats and the high genetic similarity between the Slc:Wistar and F344 inbred rats. This study demonstrates the importance of characterizing outbred rats and the need to pay ample attention to the genetic characteristics the Slc:Wistar rats for their proper use.
Aromatase, an estrogen synthase, exists in the gastric parietal cells of Wistar rats. The stomach synthesizes large amounts of estrogens and secretes them into the portal vein. We have been particularly studying gastric estrogen synthesis using Wistar rats. However, estrogen synthesis in the stomach of Sprague-Dawley (SD) rats, which are used as frequently as those of the Wistar strain, has not been clarified. We examined steroid synthesis in the stomach of SD rats using immunohistochemistry, in situ hybridization, Western blotting, real-time PCR, and LC-MS/MS. Aromatase also exists in the stomach of SD rats. Its distribution was not found to be different from that of Wistar rats. Results show that H+/K+-ATPase β-subunit and aromatase colocalized in double immunofluorescence staining. Each steroid synthase downstream from progesterone was present in the gastric mucosa. These results suggest that steroid hormones are synthesized in the parietal cells in the same pathway as Wistar rats. Although mRNA expression of steroid synthases were higher in SD, no significant difference was found in the amount of protein and each steroid hormone level in the portal vein. Although differences between strains might exist in steroid hormone synthesis, results show that SD rats are as useful as Wistar rats for gastric estrogen synthesis experimentation.
Recent studies have consistently supported the active role of blood in mediating biochemical and physiological tissue adaptations. However, no study has investigated the possible contribution of circulating factors in an exercise setting. The aim of the study was to investigate the role of circulating factors in exercise adaptations by chronically administering to sedentary animals blood plasma collected from acutely exercised animals. Phase 1: Blood plasma was collected from rats that swam to exhaustion and from sedentary rats. Phase 2: Other rats were divided into two groups (n = 20 per group): the first group involved rats that were injected intravenously with blood plasma originating from rats that previously swam to exhaustion, the second group consisted of rats that were injected intravenously with blood plasma originating from sedentary rats. Tail-vein injections (2 mL/kg) were performed daily for 21 consecutive days. Inflammatory markers (C-reactive protein, interleukins-1α, 2, 6, 8, 10 and tumor necrosis factor-a) were measured in blood plasma, muscle, and adipose tissue. Sedentary rats administered with plasma from exercised rats had significantly higher levels in all inflammatory markers measured in blood, skeletal muscle and adipose tissue, compared to the sedentary rats administered with resting plasma. Our data demonstrate that administration of "exercised" blood to sedentary rats induced inflammation in plasma, muscle and adipose tissue. Exercise adaptations are not solely due to intrinsic processes in muscle or adipose tissue. Blood factors also play a crucial role in mediating signals for tissue adaptations.
Increased motor activity is a defining characteristic of patients with ADHD, and spontaneously hypertensive rats have been suggested to be an animal model of this disorder. In the present study, we wanted to use linear and non-linear methods to explore differences in motor activity patterns in SHR/NCrl rats compared to Wistar Kyoto (WKY/NHsd) rats.
The effects of dexamethasone (DEX) on systolic blood pressure, sodium balance and the renin-angiotensin system were studied in rats. DEX significantly increased systolic blood pressure within three days of its administration, but this effect of DEX on blood pressure was not enhanced by concurrent use of saline solution. In DEX-treated rats, urine volume was significantly increased and urinary sodium excretion showed a tendency toward a slight increase compared to control rats. On the 8th day of DEX administration, plasma renin substrate (PRS) was significantly elevated compared to control rats, whereas plasma aldosterone concentration (PAC) was not significantly different from that of control rats. These results suggest that hypertension induced by DEX may not be dependent on sodium retention or activation of the renin-angiotensin system.
Minimal hepatic encephalopathy is associated with changes in the peripheral immune system which are transferred to the brain, leading to neuroinflammation and thus to cognitive and motor impairment. Mechanisms by which changes in the immune system induce cerebral alterations remain unclear. Extracellular vesicles (EVs) seem to play a role in this process in certain pathologies. The aim of this work was to assess whether EVs play a role in the induction of neuroinflammation in cerebellum and motor incoordination by chronic hyperammonemia. We characterized the differences in protein cargo of EVs from plasma of hyperammonemic and control rats by proteomics and Western blot. We assessed whether injection of EVs from hyperammonemic to normal rats induces changes in neuroinflammation in cerebellum and motor incoordination similar to those exhibited by hyperammonemic rats. We found that hyperammonemia increases EVs amount and alters their protein cargo. Differentially expressed proteins are mainly associated with immune system processes. Injected EVs enter Purkinje neurons and microglia. Injection of EVs from hyperammonemic, but not from control rats, induces motor incoordination, which is mediated by neuroinflammation, microglia and astrocytes activation and increased IL-1b, TNFα, its receptor TNFR1, NF-kB in microglia, glutaminase I, and GAT3 in cerebellum. Plasma EVs from hyperammonemic rats carry molecules necessary and sufficient to trigger neuroinflammation in cerebellum and the mechanisms leading to motor incoordination.
With the advent of genetic engineering of rodents came the need to assess fertility and germline competency, especially in chimeric rodents generated using embryonic stem cells. Traditional methods rely on natural mating and progeny testing, which is time- and cost-intensive. Electroejaculation is a faster method of collecting sperm for genetic analysis and offers the additional benefit of using fewer animals. This column describes a refined electroejaculation technique for chimeric rats using light gas anesthesia and a custom-made platform for sperm collection.
Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis.
Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and hyperlipidemia. The aim of this study was to examine the physiological difference concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker rats. We therefore measured plasma adiponectin level and analyzed adiponectin and adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined the tissue mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa) Zucker rats and lean Zucker rats, by measuring adiponectin release from these cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma agonist increased adiponectin release only from the brown adipocytes isolated from lean Zucker rats. It is the conclusive difference between obese (fa/fa) Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa) Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin level, and low expression of PPARs in BAT leads to less sensibility of adiponectin release from brown adipocytes to a PPAR gamma agonist in obese (fa/fa) Zucker rats.
The role of prolactin (PRL) in regulating the transport of the bile acid taurocholate (TC) was assessed using isolated rat hepatocytes. Na(+)-dependent TC cotransport was determined in hepatocytes from female nonpregnant, pregnant (19-20 days pregnant), postpartum (48 hr postpartum) and postpartum rats treated with bromocriptine to block PRL secretion. In separate experiments ovariectomized rats were infused i.v. with solvent alone (OVX) or with ovine PRL (100, 300 and 600 micrograms/day) for 7 days (OVX+oPRL). The least squares estimates of Km (microM) and Vmax (nmol/min/mg protein) for Na(+)-dependent TC uptake were, respectively: 15 and 1 in nonpregnant, 9 and 0.4 in pregnant, 9 and 1.1 in postpartum and 15 and 1 in bromocriptine-treated postpartum rats, and were 15 and 1 in OVX, 15 and 1 in OVX+oPRL (100 micrograms/day), 30 and 2 in OVX+oPRL (300 micrograms/day) and 18 and 2 in OVX+oPRL (600 micrograms/day) rats, respectively. Calculation of the 95% joint confidence limits for Km and Vmax showed that Na(+)-dependent TC uptake was significantly decreased in pregnant rats, and significantly increased in postpartum rats relative to nonpregnant controls. Bromocriptine-treated postpartum rats were not different from controls. Infusion of 300 and 600 micrograms/day oPRL significantly increased Na(+)-dependent TC transport relative to OVX rats. Na(+)-K(+)-ATPase activity did not differ among the groups. These data indicate that PRL is responsible for the increased Na(+)-dependent transport of TC in the maternal liver postpartum, and that administration of oPRL to ovariectomized rats increases this transport in a dose-dependent manner.
Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males.
To investigate whether the classic bystander effect is unique to humans, the effect of bystanders on rat helping was studied. In the presence of rats rendered incompetent to help through pharmacological treatment, rats were less likely to help due to a reduction in reinforcement rather than to a lack of initial interest. Only incompetent helpers of a strain familiar to the helper rat exerted a detrimental effect on helping; rats helped at near control levels in the presence of incompetent helpers from an unfamiliar strain. Duos and trios of potential helper rats helped at superadditive rates, demonstrating that rats act nonindependently with helping facilitated by the presence of competent-to-help bystanders. Furthermore, helping was facilitated in rats that had previously observed other rats' helping and were then tested individually. In sum, the influence of bystanders on helping behavior in rats features characteristics that closely resemble those observed in humans.
The purpose of this study is to establish a protocol of retention-enema experiments and evaluate the antihypertensive effect and the safety of Gwakhyangjeonggi-san retention enema. Normal and spontaneously hypertensive rats (SHRs) were divided into treatment and control groups, respectively. We applied the Gwakhyangjeonggi-san extract by decoction and 0.9% NaCl in each group, estimated the blood pressure and body weight, and performed HPLC analysis. ALT, AST, BUN, and creatinine were examined. The systolic blood pressure within each group in normal rats differed significantly in time effect, and so did the diastolic blood pressure in the treatment group of normal rats. The systolic, diastolic, and mean blood pressure showed significant differences in group effect in the treatment group of the SHRs. The time effect of the body weight in both groups of normal rats differed significantly, so did group × time and time effects in both groups of SHRs. AST, ALT, BUN, and creatinine showed no significant difference between groups. We concluded that the Gwakhyangjeonggi-san retention enema has a hypotensive effect in normal rats within the regular range of blood pressure, but an antihypertensive effect in SHRs. Also, the intervention is safe and does not affect the liver and kidney functions in normal rats.
Acetylcholine (ACh) is a novel antihypertensive food component. Here, we demonstrate the differential effects of oral ACh on high and normal blood pressure in rats. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were administered ACh orally. The blood pressure and heart rate of SHRs were significantly lowered with ACh doses of 10-5 and 10-3 mol/kg body weight (b.w.), and the urinary catecholamine levels were significantly decreased with 10-3 mol/kg b.w. In contrast, oral ACh administration had no effect on WKY rats. This difference was likely caused by differences in sympathetic nervous activity and the baroreflex between strains. Comparison of gene sequences between the two strains revealed Chga mutations, suggesting that changes in the expression of chromogranin A might be involved in the baroreflex in SHRs. Oral ACh had an antihypertensive effect under hypertension but not normotension, indicating that this may be used safely to prevent hypertension.
Not including female rats or mice in neuroscience research has been justified due to the variable nature of female data caused by hormonal fluctuations associated with the female reproductive cycle. In this study, we investigated whether female rats are more variable than male rats in scientific reports of neuroscience-related traits.
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