Laboratory Rodents (laboratory + rodents)

Distribution by Scientific Domains

Selected Abstracts


EVOLUTION, Issue 3 2000
Daryl P. Shanley
Abstract., The disposable soma theory suggests that aging occurs because natural selection favors a strategy in which fewer resources are invested in somatic maintenance than are necessary for indefinite survival. However, laboratory rodents on calorie-restricted diets have extended life spans and retarded aging. One hypothesis is that this is an adaptive response involving a shift of resources during short periods of famine away from reproduction and toward increased somatic maintenance. The potential benefit is that the animal gains an increased chance of survival with a reduced intrinsic rate of senescence, thereby permitting reproductive value to be preserved for when the famine is over. We describe a mathematical life-history model of dynamic resource allocation that tests this idea. Senescence is modeled as a change in state that depends on the resources allocated to maintenance. Individuals are assumed to allocate the available resources to maximize the total number of descendants. The model shows that the evolutionary hypothesis is plausible and identifies two factors, both likely to exist, that favor this conclusion. These factors are that survival of juveniles is reduced during periods of famine and that the organism needs to pay an energetic "overhead" before any litter of offspring can be produced. If neither of these conditions holds, there is no evolutionary advantage to be gained from switching extra resources to maintenance. The model provides a basis to evaluate whether the life-extending effects of calorie-restriction might apply in other species, including humans. [source]

A hitchhiker's guide to behavioral analysis in laboratory rodents

N. Sousa
Genes and environment are both essential and interdependent determinants of behavioral responses. Behavioral genetics focuses on the role of genes on behavior. In this article, we aim to provide a succinct, but comprehensive, overview of the different means through which behavioral analysis may be performed in rodents. We give general recommendations for planning and performing behavioral experiments in rats and mice, followed by brief descriptions of experimental paradigms most commonly used for the analysis of reflexes, sensory function, motor function and exploratory, social, emotional and cognitive behavior. We end with a discussion of some of the shortcomings of current concepts of genetic determinism and argue that the genetic basis of behavior should be analyzed in the context of environmental factors. [source]

Immunoblot Analysis as an Alternative Method to Diagnose Enterohepatic Helicobacter Infections

HELICOBACTER, Issue 3 2009
Torkel Wadström
Abstract Introduction: Enterohepatic Helicobacter species have been associated with chronic infections of the hepatobiliary tract and lower bowel in naturally and experimentally infected mice, Helicobacter -infected animals should thus not be used in studies of diseases associated with chronic inflammation. Helicobacter species induce inflammation and modulate host immune responses, thus emphasizing the need to diagnose these infections in laboratory animals. Materials and Methods: An immunoblot assay was developed to analyze antibodies to enterohepatic Helicobacter species in naturally colonized laboratory mouse colonies. We evaluated the serum antibody responses to cell surface proteins of H. bilis, H. hepaticus, and H. ganmani in 188 mouse sera from four different university animal facilities. Lower bowel tissue specimens from 56 of these animals were available and analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and the results compared with matched immunoblot patterns. Results: Specific antibody reactivity to H. bilis was detected in 8 of 186 (4.3%) sera, to H. hepaticus in 45 of 184 (24%) sera, and to H. ganmani in 51 of 188 (27%) of tested sera. These results were compared with PCR-DGGE analyses of tissue samples of corresponding animals, and concordance between the two diagnostic tests was found in 96% for H. bilis, in 91% for H. hepaticus, and in 82% for H. ganmani. The PCR-DGGE also detected DNA of H. typhlonius, H. sp. flexispira, and H. rodentium. Conclusions: Infection with enterohepatic species was common in the laboratory mouse colonies tested, independent of strain and stock. Immunoblot analysis seems to be a promising diagnostic tool to monitor enterohepatic Helicobacter species infections of laboratory rodents. [source]

Effect of aging on neurogenesis in the canine brain

AGING CELL, Issue 3 2008
Anton Pekcec
Summary An age-dependent decline in hippocampal neurogenesis has been reported in laboratory rodents. Environmental enrichment proved to be a strong trigger of neurogenesis in young and aged laboratory rodents, which are generally kept in facilities with a paucity of environmental stimuli. These data raise the question whether an age-dependent decline in hippocampal cell proliferation and neurogenesis can also be observed in individuals exposed to diversified and varying surroundings. Therefore, we determined rates of canine hippocampal neurogenesis using post-mortem tissue from 37 nonlaboratory dogs that were exposed to a variety of environmental conditions throughout their life. Expression of the neuronal progenitor cell marker doublecortin clearly correlated with age. The analysis of doublecortin-labeled cells in dogs aged > 133 months indicated a 96% drop in the aged canine brain as compared to young adults. Expression of the proliferation marker Ki-67 in the subgranular zone decreased until dogs were aged 85,132 months. In the aging canine brain amyloid-beta peptide deposits have been described that might resemble an early pathophysiological change in the course of human Alzheimer's disease. Comparison of Ki-67 and doublecortin expression in canine brain tissue with or without diffuse plaques revealed no differences. The data indicate that occurrence of diffuse plaques in the aging brain is not sufficient to trigger enhanced proliferation or enhanced neurogenesis such as described in human Alzheimer's disease. In addition, this study gives first proof that an age-dependent decline also dominates hippocampal neurogenesis rates in individuals living in diversified environments. [source]

Does caloric restriction extend life in wild mice?

AGING CELL, Issue 6 2006
James M. Harper
Summary To investigate whether mice genetically unaltered by many generations of laboratory selection exhibit similar hormonal and demographic responses to caloric restriction (CR) as laboratory rodents, we performed CR on cohorts of genetically heterogeneous male mice which were grandoffspring of wild-caught ancestors. Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory-adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups, although a maximum likelihood fitted Gompertz mortality model indicated a significantly shallower slope and higher intercept for the CR group. This result was due to higher mortality in CR animals early in life, but lower mortality late in life. A subset of animals may have exhibited the standard demographic response to CR in that the longest-lived 8.1% of our animals were all from the CR group. Despite the lack of a robust mean longevity difference between groups, we did note a strong anticancer effect of CR as seen in laboratory rodents. Three plausible interpretations of our results are the following: (1) animals not selected under laboratory conditions do not show the typical CR effect; (2) because wild-derived animals eat less when fed AL, our restriction regime was too severe to see the CR effect; or (3) there is genetic variation for the CR effect in wild populations; variants that respond to CR with extended life are inadvertently selected for under conditions of laboratory domestication. [source]

Palatable High-Energy Diet Decreases the Expression of Cannabinoid Type 1 Receptor Messenger RNA in Specific Brain Regions in the Rat

E. Timofeeva
In laboratory rodents, a palatable high-energy diet (PHED) is usually consumed in a higher quantity than a standard laboratory diet, leading to the development of an obese phenotype. The central effects of PHED are not fully understood. Nonetheless, the long-term consumption of PHED can decrease cannabinoid type 1 receptor (CB1R) protein density in particular brain regions. However, little is known about the diet-dependent regulation of the brain expression of CB1R mRNA. The present study aimed to investigate the effects of the long-term consumption of PHED and short-term (12 h) food deprivation on the brain expression of CB1R mRNA. For 13 weeks, rats were fed a standard laboratory chow or PHED presented as a free choice of chow, shortcake biscuits and pork spread. In total, the food intake of PHED rats was higher than that of chow-fed animals. Expectedly, PHED rats demonstrated higher body weight than chow-fed animals. The difference in body weight between PHED- and chow-fed rats was as result of the fat but not the lean mass. PHED-fed rats had significantly higher plasma levels of leptin and insulin and significantly higher levels of expression of suppressor of cytokine signalling 3 (SOCS-3) in the arcuate hypothalamic nucleus. The long-term consumption of PHED significantly decreased the levels of CB1R mRNA expression in the cingulate (Cg) cortex, ventromedial hypothalamic nucleus and the descending/autonomic divisions of the parvocellular hypothalamic nucleus (PVH), the ventrolateral parvocellular PVH and, to a lesser extent, the dorsomedial parvocellular PVH. Acute food deprivation decreased the levels of CB1R transcript in the Cg and ventrolateral parvocellular PVH. Altogether, the present results demonstrate that long-term PHED leads to an increase in the hypothalamic expression of SOCS-3 mRNA and a decrease in expression of CB1R mRNA in the Cg cortex and specific hypothalamic regions. [source]

Period 2 Gene Deletion Abolishes ,-Endorphin Neuronal Response to Ethanol

ALCOHOLISM, Issue 9 2010
Maria Agapito
Background:, Ethanol exposure during early life has been shown to permanently alter the circadian expression of clock regulatory genes and the ,-endorphin precursor proopiomelanocortin (POMC) gene in the hypothalamus. Ethanol also alters the stress- and immune-regulatory functions of ,-endorphin neurons in laboratory rodents. Our aim was to determine whether the circadian clock regulatory Per2 gene modulates the action of ethanol on ,-endorphin neurons in mice. Methods:,Per2 mutant (mPer2Brdml) and wild type (C57BL/6J) mice were used to determine the effect of Per2 mutation on ethanol-regulated ,-endorphin neuronal activity during neonatal period using an in vitro mediobasal hypothalamic (MBH) cell culture model and an in vivo milk formula feeding animal model. The ,-endorphin neuronal activity following acute and chronic ethanol treatments was evaluated by measuring the peptide released from cultured cells or peptide levels in the MBH tissues, using enzyme-linked immunosorbent assay (ELISA). Results:,Per2 mutant mice showed a higher basal level of ,-endorphin release from cultured MBH cells and a moderate increase in the peptide content in the MBH in comparison with control mice. However, unlike wild type mice, Per2 mutant mice showed no stimulatory or inhibitory ,-endorphin-secretory responses to acute and chronic ethanol challenges in vitro. Furthermore, Per2 mutant mice, but not wild type mice, failed to show the stimulatory and inhibitory responses of MBH ,-endorphin levels to acute and chronic ethanol challenges in vivo. Conclusions:, These results suggest for the first time that the Per2 gene may be critically involved in regulating ,-endorphin neuronal function. Furthermore, the data revealed an involvement of the Per2 gene in regulating ,-endorphin neuronal responses to ethanol. [source]

Use of Genetic Analyses to Refine Phenotypes Related to Alcohol Tolerance and Dependence

ALCOHOLISM, Issue 2 2001
John C. Crabbe
Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly. [source]

EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells

Chi-Hung Huang
Abstract In the previous studies, (,)-epigallocatechin-3-gallate (EGCG) has been shown to have anticarcinogenic effects via modulation in protein expression of p53. Using p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of EGCG resulted in dose-dependent inhibition of cellular proliferation, which suggests that the interaction of EGCG with p53 may not fully explain its inhibitory effect on proliferation. Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents. EGCG has multiple beneficial activities similar to those associated with CR. One key enzyme thought to be activated during CR is AMP-activated kinase (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated AMPK in both p53 positive and negative human hepatoma cells. The activation of AMPK suppressed downstream substrates, such as mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and a general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the decision between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based on these results, we have demonstrated that EGCG has a potential to be a chemoprevention and anti-lipogenesis agent for human hepatoma cells. [source]

The Immunohistochemical Localization of Desmin and Smooth Muscle Actin in the Ovary of the African Giant Rat (Cricetomys gambianus) During the Oestrous Cycle

M.-C. Madekurozwa
Summary The aim of this study was to describe the distribution of smooth muscle actin and desmin immunopositive cells in the ovary of the giant rat. In addition, the study describes the morphological changes in the ovary of this species during the oestrous cycle. Healthy secondary and tertiary follicles dominated the ovary during pro-oestrus and oestrus. The theca externa of the tertiary follicles was immunopositive for smooth muscle actin, but immunonegative for desmin. Oestrus was also characterized by the presence of corpora haemorrhagica, which had an outer layer of smooth muscle actin immunopositive cells. Differentiating corpora lutea were observed during metoestrus. A further notable feature of the ovary during metoestrus was the presence of numerous atretic secondary and tertiary follicles. In the later stages of atresia, the follicles were infiltrated by desmin and smooth muscle actin immunopositive cells. Dioestrus was characterized by the presence of non-regressing and regressing corpora lutea. Immunostaining for smooth muscle actin was demonstrated in the enclosing layer of the corpora lutea, as well as in the tunica media of blood vessels within the corpora lutea. The results of this study have shown that morphological changes in the ovary of the giant rat during the oestrus cycle are similar to those of laboratory rodents. Furthermore, the results of the immunohistochemical study indicate that the perifollicular distribution of desmin and smooth muscle actin cells changes during follicular development and atresia. [source]

A Pressure-controlled Rat Ventilator With Electronically Preset Respirations

Valentin L. Ordodi
Abstract:, Major experimental surgery on laboratory animals requires adequate anesthesia and ventilation to keep the animal alive throughout the procedure. A ventilator is a machine that helps the anesthesized animal breathe through an endotracheal tube by pumping a volume of gas (oxygen, air, or other gaseous mixtures), comparable with the normal tidal volume, into the animal's lungs. There are two main categories of ventilators for small laboratory rodents: volume-controlled and pressure-controlled ones. The volume-controlled ventilator injects a preset volume into the animal's lungs, no matter the airways' resistance (with the peak inspiratory pressure allowed to vary), while the pressure ventilator controls the inspiratory pressure and allows the inspiratory volume to vary. Here we show a rat pressure ventilator with a simple expiratory valve that allows gas delivery through electronic expiration control and offers easy pressure monitoring and frequency change during ventilation. [source]

Chlorpyrifos-Induced Hypothermia and Vasodilation in the Tail of the Rat: Blockade by Scopolamine,

Christopher J. Gordon
Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25°. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t) concomitant with a 0.5° reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS. [source]