Mice In Cages Research Articles

Estrogen supplementation increases renal sodium absorption during high salt consumption in female and male mice

The purpose of this study was to determine the effects of estrogen supplementation on the renal excretion of Na+ (UNa· V) in CD‐1 mice. Two studies were conducted – one with females and one with males. Female groups (n=4/group) included normal (NF), ovariectomized implanted with a placebo pellet (OP), and ovariectomized with a 0.1 mg estrogen pellet (OE). Male groups included normal (NM), castrated with placebo pellet (CP), and castrated with estrogen pellet (CE). Pellets were purchased from Innovative Research of America (Sarasota, FL). Mice in metabolic cages consumed 1% salt diet for 5 days, 4% salt for the next 15 days, and 1% salt for the final 5 days. No differences occurred during the 1% salt periods. Average UNa· V (μEq/day ± se) for the 4% salt periods were: females: 1652±92, 2011±82*, 1457±106† (NF, OP, OE, respectively); and males: 1976±163, 2154±153, 1312±100*† (NM, CP, CE, respectively) (*p<.01 compared to NF or NM; † ‐ p<0.01 compared to OP or CP). We conclude that estrogen administration yields significant renal Na+ absorption during high salt loads in female and male mice. Results suggest a sex difference in Na+ excretion during high salt consumption.

Cage-induced stereotypies, perseveration and the effects of environmental enrichment in laboratory mice

When kept in barren and restrictive cages, animals frequently develop stereotypic behaviour patterns that are characterized by high repetition rates, conspicuous invariance and an apparent lack of function. Although millions of animals are affected, the underlying causes and mechanisms are still unclear. Growing evidence suggests that cage-induced stereotypies may reflect pathological dysfunction within basal ganglia circuitry expressed by perseverative behaviour. In order to assess whether variation in stereotypy performance and variation in perseverative behaviour may have a common cause in ICR CD-1 mice, we assessed the effects of environmental enrichment on both phenomena. We raised 48 female ICR CD-1 mice in standard or enriched cages from three weeks to either 6 or 11 months of age and measured stereotypy level in the home cage and perseveration on an extinction task. We further examined whether enriched rearing conditions (early enrichment) protect mice from the developing stereotypies later in life and whether stereotypies developed in barren cages would persist in an enriched environment (late enrichment) by transferring standard mice to enriched cages and vice versa for 14 weeks after completion of the extinction task. We found no evidence for a causal relation between stereotypy and perseveration in mice. However, transfer to enriched cages reduced stereotypy levels significantly both at 6 and 11 months of age indicating that stereotypies had not become established yet. Finally, we found that removing enrichments at both ages did not induce higher stereotypy levels, thereby confirming earlier reports of a neuroprotective effect of early enrichment.

Urine from Sexually Mature Intact Male Mice Contributes to Increased Cardiovascular Responses during Free-Roaming and Restrained Conditions

Pheromones in the urine regulate aggression of male mice and castrated males produce less of these pheromones. We tested the hypothesis that pheromones in the urine of sexually mature-intact (SMI) males placed in the cage bedding of an individually housed male mouse or in a mouse restrainer would contribute to a significant increase in mean arterial pressure (MAP), heart rate (HR), and activity. Sexually mature male C57BL/6 mice were implanted with a biotelemetry transmitter to measure MAP, HR, and activity. Urine (200 μL) from SMI mice placed in the cages of singularly housed male mice caused significant changes above baseline values for MAP (21 ± 4 mmHg), HR (145 ± 25 bpm), and activity (9 ± 2 counts) when compared to urine from castrated mice-induced MAP (11 ± 3 mmHg), HR (70 ± 15 bpm), and activity (5 ± 1 counts). Pretreatment with terazosin significantly reduced the change in MAP (9 ± 3 mmHg), heart rate (90 ± 15 bpm), and activity (4 ± 2 counts) responses to urine from SMI males. Saline did not significantly increase MAP, HR, or activity in any group. During restraint, urine from SMI mice caused a significant change in MAP (5 ± 0.4 mmHg) and HR (17 ± 1 bpm); urine from castrated mice did not cause a significant increase in MAP and HR. Our results demonstrate that a significant increase in MAP, HR, and activity occurs when male mice are exposed to urine pheromones from SMI males. In summary, pheromones in the urine of SMI male excreted in the cage bedding and mouse restrainers contribute to a significant increase in cardiovascular responses in the absence of direct physical contact with a different male mouse or animal handler.

Epigenetics for ecotoxicologists

Do genes define your destiny? The field of epigeneticsexamines how genes and the environment interact to formthe basis of heredity and comes up with some surprisingfindings. We often think of deoxyribonucleic acid (DNA) asthe sole physical basis for heredity, the genetic code thatdetermines everything from eye and hair color to specificpersonality traits. The growing field of epigenetics suggeststhat this traditional paradigm is an oversimplification. Epi-genetics is the study of factors that are heritable, but whichoccur by mechanisms other than changes in the DNA codeitself. C.H. Waddington first used the term epigenetics in theearly 1940s to describe ‘‘the interactions of genes with theirenvironment, which bring the phenotype into being.’’ Epi-genetic marks are susceptible to environmental influences—both chemical and nonchemical—and can be inherited inways that may seem counterintuitive (see sidebar, ExpandingIdeas About Biological Inheritance). Effects of early lifeexperiences, such as parental care or nutrition, can showup later in life and even be passed on to future generations.This emerging area of research has interesting and importantimplications for the field of ecotoxicology—from basicscience to international policy.In classic genetics, genetic material is in the form of DNAand encodes all of the information necessary for life. Thisinformation is copied faithfully and passed down as cellsdivide. Every cell contains a complete copy of the DNAcode, but the pattern of gene expression—that is, whichgenes are turned ‘‘on’’ (expressed) or ‘‘off’’ (nonex-pressed)—determines the cell type and function. A skin cellon your arm contains the same DNA code as a nerve cell inyour brain, but their extreme differences in structure andfunction are due to the particular set of genes that each isexpressing. Epigenetics refers to an annotation in the form ofchemical marks on top of the DNA code; the prefix ‘‘epi’’comesfromaGreekwordmeaning‘‘over’’or‘‘above.’’Thesechemical marks, which are discussed in detail below, affectwhich genes are expressed and at what levels. Epigeneticmarks are highly influenced by the environment and can beinherited along with the genetic code as cells divide mitoti-cally, and in some cases meiotically, from one generation tothe next.Epigenetics is receiving significant attention in the field ofbiomedicine. A PubMed search for ‘‘epigenetic’’ revealedthat more than 1,300 review articles have been written on thetopic, of which more than 50% were published in the lastthree years alone. Epigenetics provides a mechanism for theBarker hypothesis, which postulates that nutrition and otherenvironmentalfactorsearlyindevelopmentcanaltersuscept-ibility to chronic diseases in adulthood. A classic exampleof this is that individuals who were conceived during theDutchWinterHunger(1944–1945)havepersistentepigeneticalterations on a characteristic gestational marker, the IGF2gene, as adults. Furthermore, individuals who experiencedthe Dutch Winter Hunger have higher rates of metabolicdisorders and cardiovascular disease, the epigenetic mecha-nisms of which are the focus of ongoing studies. Nutritionaldeprivation may also have an impact on human longevity;indeed, lifespanisnegativelycorrelated withfoodabundance

Prostaglandin E 2 produced by microsomal prostaglandin E synthase-1 regulates the onset and the maintenance of wakefulness

This study examined the effect of prostaglandin E 2 (PGE 2) produced by microsomal prostaglandin E synthase-1 (mPGES-1) on circadian rhythm. Using wild-type mice (WT) and mPGES-1 knockout mice ( mPGES-1 −/−), I recorded and automatically analyzed the natural behavior of mice in home cages for 24 h and measured brain levels of PGE 2. The switch to wakefulness was not smooth, and sleepiness and the total duration of sleep were significantly longer in the mPGES-1 −/− mice. Moreover, the basal concentration of PGE 2 was significantly lower in the mPGES-1 −/− mice. These findings suggest that PGE 2 produced by mPGES-1 regulates the onset of wakefulness and the maintenance of circadian rhythm.

Eszopiclone facilitation of the antidepressant efficacy of fluoxetine using a social defeat stress model

This study analyzed the interaction of the sleep aid eszopiclone (ESZ) and antidepressant fluoxetine (FLX) on social defeat stress (SDS) in the mouse. Beta adrenoreceptors, brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) expression in the hippocampus and frontal cortex were also analyzed. Subjects were adult male ‘intruder’ C57/B6 mice that were exposed to a retired ‘resident’ male breeder ICR mouse in this animal's home cage for a 5min period for each of 10 consecutive days, and the resident established physical dominance. The following day, all animals were assigned to one of four drug treatment groups, and treatment was given for up to 18days: vehicle, ESZ only (3mg/kg), FLX (10mg/kg) only, or ESZ+FLX. A social interaction test was given on days 1, 5, 10, and 15 of drug treatment to assess SDS. Results showed that the ESZ+FLX group spent less time in avoidance zones during the interaction test at days 1 and 5, and more time in the interaction zone at day 5 compared to defeated mice given vehicle. All drug treatment groups spent more time in the interaction zone compared to defeated mice given vehicle on day 1 as well as day 10. SDS completely dissipated by the fourth interaction test according to both behavioral measures. Neurochemically, SDS did not produce changes in any marker analyzed. This study shows the combination of ESZ and FLX alleviated SDS, but a neurochemical correlate remains elusive.

Gender Differences in Locomotor and Stereotypic Behavior Associated With l-Carnitine Treatment in Mice

The carnitines exert neuroprotective and neuromodulatory actions, and carnitine supplementation increases locomotor activity (LMA) in experimental animals. We measured 13 indexes of LMA and 3 indexes of stereotypic activity (STA) in adult male and female caged mice. In a randomized 4-week trial, 10 males and 10 females received 50 mg/kg body weight PO l-carnitine, and another 10 males and 10 females received placebo. Compared with placebo-treated females, placebo-treated males had a greater number of stereotypies (NSTs), stereotypy counts (STCs), stereotypy time (STT), and right front time (RFT), but smaller total distance traveled (TDT), margin distance (MD), number of vertical movements (NVMs), and left rear time (LRT). Compared with placebo-treated males, carnitine-treated males had greater horizontal activity (HA), movement time (MT), NVM, STT, TDT, STC, MD, LRT, and clockwise revolutions (CRs), but smaller left front time (LFT) and RFT. Compared with placebo-treated females, carnitine-treated females had greater NST, STC, STT, LFT, and RFT, but smaller NM, HA, NVM, VA, MT, anticlockwise revolutions (ACRs), CR, TDT, and MD; right rear time (RRT) remained statistically insignificant across all comparisons. In summary, l-carnitine caused gender differences to persist for STC, diminish for NST and STT, disappear for LRT and NVM, change in the opposite direction for TDT and MD, appear de novo for HA, VA, NM, MT, and LFT, and remain absent for RRT and ACR. Some indexes of LMA and STA are sexually dimorphic in adult mice, and l-carnitine differentially maintains, diminishes/cancels, inverts, or creates the sexual dimorphism of particular indexes.

Increased Voluntary Running in PAS Kinase-knockout Mice

PAS kinase (PASK) deletion in mice leads to increased oxidative metabolism, increased ATP production, and protection from diet-induced obesity. The role that PASK plays in exercise metabolism and performance is not known. PURPOSE: To assess voluntary running capacity and muscle expression of proteins related to metabolism in PASK knockout (KO) mice. METHODS: Voluntary running of female KO and littermate wild-type mice (n=4/group) was assessed in cages equipped with computer-monitored wheels. Mice in cages without wheels served as sedentary controls. After 3 weeks of voluntary run training, heart and triceps were excised and immediately frozen. Western blot (WB) analysis was performed for cytochrome C, phospho-AMPK, and phospho-ACC. RESULTS: KO mice ran 39% more than WT mice over the course of the 3-week running period (9513 ± 144 m/day vs. 6852 ± 829 m/day). No differences in AMPK phosphorylation were observed in the heart or triceps, but ACC phosphorylation was elevated in sedentary KO hearts (27% greater than in WT). Cytochrome C levels in sedentary mice were 40% higher in KO compared to WT mice, and increased with training in both genotypes (62% increase in WT; 28% increase in KO). No significant differences in cytochrome C levels were observed in the heart. CONCLUSIONS: PASK negatively impacts voluntary running performance in mice. Elevated cytochrome C levels in the triceps of PASK-KO mice suggest that increased oxidative capacity in skeletal muscle may contribute to the increased running performance in PASK-KO mice.

Responses to environmental enrichment differ with sex and genotype in a transgenic mouse model of Huntington's disease.

BackgroundEnvironmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival.Methodology/Principal FindingsWe examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an “enriched” environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The “home cage” and “playground” groups were subdivided into “handling” (stimulated throughout the experimental period) and “no-handling” groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice.Conclusions/SignificanceWe show that even when mice are living in an enriched home cage, further EE had beneficial effects. However, the improvements in cognition and survival vary with sex and genotype. These results indicate that EE may improve the quality of life of HD patients, but we suggest that EE as a therapy should be tailored to individuals.

Microglial activation as a measure of stress in mouse brains exposed acutely (60 minutes) and long-term (2 years) to mobile telephone radiofrequency fields

To determine whether acute or long-term exposure of the brain to mobile telephone radiofrequency (RF) fields produces activation of microglia, which normally respond rapidly to any change in their microenvironment. Using a purpose designed exposure system at 900 MHz, mice were given a single, far-field whole body exposure at a specific absorption rate (SAR) of 4 W/kg for 60 min (acute) or on five successive days per week for 104 weeks (long-term). Control mice were sham-exposed or freely mobile in a cage to control for any stress caused by immobilisation in the exposure module. Positive control brains subjected to a stab wound were also included to confirm the ability of microglia to react to any neural stress. Brains were perfusion-fixed with 4% paraformaldehyde and representative regions of the cerebral cortex and hippocampus immunostained for ionised calcium binding adaptor molecule (Iba1), a specific microglial marker. There was no increase in microglial Iba1 expression in brains short or long-term exposed to mobile telephony microwaves compared to control (sham-exposed or freely moving caged mice) brains, while substantial microglial activation occurred in damaged positive control neural tissue. Acute (60 minutes) or longer duration (2 years) exposure of murine brains to mobile telephone RF fields did not produce any microglial activation detectable by Iba1 immunostaining.

Laboratory Rodent Welfare: Thinking Outside the Cage

This commentary presents the case against housing rats and mice in laboratory cages; the commentary bases its case on their sentience, natural history, and the varied detriments of laboratory conditions. The commentary gives 5 arguments to support this position: (a) rats and mice have a high degree of sentience and can suffer, (b) laboratory environments cause suffering, (c) rats and mice in the wild have discrete behavioral needs, (d) rats and mice bred for many generations in the laboratory retain these needs, and (e) these needs are not met in laboratory cages.

Expression of the water channel protein, aquaporin-4, in mouse brains exposed to mobile telephone radiofrequency fields

To determine whether exposure to mobile telephone radiofrequency (RF) fields, either acutely or long-term, produces up-regulation of the water channel protein, aquaporin-4 (AQP-4). Using a purpose-designed exposure system at 900 MHz, mice were given a single, far-field whole body exposure at a specific absorption rate of 4 W/kg for 60 minutes or a similar exposure on 5 successive days/week for 104 weeks. Control mice were sham-exposed or freely mobile in a cage to control for any stress caused by restraint in the exposure module. A positive control group was given a clostridial toxin known to cause microvascular endothelial injury, severe vasogenic oedema and upregulation of AQP-4. Brains were perfusion fixed with 4% paraformaldehyde, coronal sections cut from six levels, and immunostained for the principal water channel protein in brain, AQP-4. There was no increase in AQP-4 expression in brains exposed to mobile phone microwaves compared to control (sham exposed and freely moving caged mice) brains after short or protracted exposure, while AQP-4 was substantially upregulated in the brains of mice given the clostridial toxin. Brains exposed to mobile telephone RF fields for a short (60 minutes) or long (2 years) duration did not show any immunohistochemically detectable up-regulation of the water channel protein, AQP-4, suggesting that there was no significant increase in blood-brain barrier permeability

Voluntary exercise induces anxiety‐like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis

Several studies investigated the effect of physical exercise on emotional behaviors in rodents; resulting findings however remain controversial. Despite the accepted notion that voluntary exercise alters behavior in the same manners as antidepressant drugs, several studies reported opposite or no effects at all. In an attempt to evaluate the effect of physical exercise on emotional behaviors and brain plasticity, we individually housed C57BL/6J male mice in cages equipped with a running wheel. Three weeks after continuous voluntary running we assessed their anxiety- and depression-like behaviors. Tests included openfield, dark-light-box, elevated O-maze, learned helplessness, and forced swim test. We measured corticosterone metabolite levels in feces collected over a 24-h period and brain-derived neurotrophic factor (BDNF) in several brain regions. Furthermore, cell proliferation and adult hippocampal neurogenesis were assessed using Ki67 and Doublecortin. Voluntary wheel running induced increased anxiety in the openfield, elevated O-maze, and dark-light-box and higher levels of excreted corticosterone metabolites. We did not observe any antidepressant effect of running despite a significant increase of hippocampal neurogenesis and BDNF. These data are thus far the first to indicate that the effect of physical exercise in mice may be ambiguous. On one hand, the running-induced increase of neurogenesis and BDNF seems to be irrelevant in tests for depression-like behavior, at least in the present model where running activity exceeded previous reports. On the other hand, exercising mice display a more anxious phenotype and are exposed to higher levels of stress hormones such as corticosterone. Intriguingly, numbers of differentiating neurons correlate significantly with anxiety parameters in the openfield and dark-light-box. We therefore conclude that adult hippocampal neurogenesis is a crucial player in the genesis of anxiety.

Major Urinary Protein-1 Increases Energy Expenditure and Improves Glucose Intolerance through Enhancing Mitochondrial Function in Skeletal Muscle of Diabetic Mice

Major urinary protein-1 (MUP-1) is a low molecular weight secreted protein produced predominantly from the liver. Structurally it belongs to the lipocalin family, which carries small hydrophobic ligands such as pheromones. However, the physiological functions of MUP-1 remain poorly understood. Here we provide evidence demonstrating that MUP-1 is an important player in regulating energy expenditure and metabolism in mice. Both microarray and real-time PCR analysis demonstrated that the MUP-1 mRNA abundance in the liver of db/db obese mice was reduced by approximately 30-fold compared with their lean littermates, whereas this change was partially reversed by treatment with the insulin-sensitizing drug rosiglitazone. In both dietary and genetic obese mice, the circulating concentrations of MUP-1 were markedly decreased compared with the lean controls. Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance. At the molecular level, MUP-1-mediated improvement in metabolic profiles was accompanied by increased expression of genes involved in mitochondrial biogenesis, elevated mitochondrial oxidative capacity, decreased triglyceride accumulation, and enhanced insulin-evoked Akt signaling in skeletal muscle but not in liver. Altogether, these findings raise the possibility that MUP-1 deficiency might contribute to the metabolic dysregulation in obese/diabetic mice, and suggest that the beneficial metabolic effects of MUP-1 are attributed in part to its ability in increasing mitochondrial function in skeletal muscle.

Pheromones Produced by the Intact Male Mouse causes a Hypertensive Response during Restrained and Free‐Roaming conditions

Pheromones regulate aggression in sexually mature male mice and castrated males no longer produce these pheromones. We tested the hypothesis that pheromones from the urine of sexually mature‐intact (SMI) males placed in a restrainer or in cage bedding would elicit a hypertensive response in male mice. Sexually mature male C57BL/6 mice were implanted with a biotelemetry device to measure mean arterial pressure (MAP), heart rate (HR) and locomotor activity. All groups were exposed to 200 μl of urine from SMI males, castrated mice and saline. Urine from SMI mice placed in the cages caused a peak change in MAP (24 + 5 mmHg), HR (151 + 25 bpm) and activity (11 + 3 counts). Urine from castrated mice caused a peak change in MAP (12 + 5 mmHg), HR (93 + 15 bpm), and activity (7 + 1 counts). Saline did not increase MAP, HR or activity in any group. During restraint, urine from SMI mice caused a peak change in MAP (19 + 3 mmHg), HR (159 + 27 bpm). Urine from castrated mice caused a peak change in MAP (9 + 2 mmHg), HR (75 + bpm). Saline elicited a peak change in MAP (4 + 1 mmHg) and HR (20 + 7 bpm). These results indicate that a significant pressor response occurs when male mice are exposed to urine from SMI males. Therefore, the SMI male pheromones excreted in the cage bedding and mouse restrainers are responsible for significant increases in the pressor response.

Ammonia and carbon dioxide concentrations in disposable and reusable static mouse cages

The value of a static mouse cage is partially determined by the cage's ability to dissipate carbon dioxide and ammonia. The authors compared the concentrations of ammonia and carbon dioxide produced by mice housed in two types of static isolator cages: a newly introduced disposable cage and a conventional reusable cage. Female mice were housed in three disposable and three reusable cages (n = 5 per cage). After 7 d, groups that were housed in disposable cages were rehoused in fresh reusable cages and vice versa. Intracage carbon dioxide, ammonia, temperature and relative humidity were measured daily. Overall, there were no significant differences in carbon dioxide or ammonia concentrations between the cage types. Within 30 min of placing mice in cages, carbon dioxide concentrations rose to more than 10,000 ppm in both cage types and rarely dropped below 8,000 ppm during both phases of the study. Ammonia concentrations rose slowly until day 4 and then began to rise rapidly. The maximum average ammonia concentration was 710 ppm. There was a highly significant relationship between increasing levels of humidity and ammonia production in the disposable cages (r = 0.88). For the reusable cages, the correlation was not as strong (r = 0.68). Both cage types were similar in their ability to dissipate carbon dioxide and ammonia. The suggested frequency of cage changing can only be estimated; on the basis of existing literature, it seems prudent to change cages when the ammonia concentration reaches 50 ppm.

Sex and genotype differences in a transgenic mouse model of Huntington's disease in response to environmental enrichment

Event Abstract Back to Event Sex and genotype differences in a transgenic mouse model of Huntington's disease in response to environmental enrichment Nigel I. Wood1*, Elizabeth A. Skillings1, Catherine J. McAllister1, Valentina Carta1 and A. J. Morton1 1 University of Cambridge, Department of Pharmacology, United Kingdom Environmental enrichment in normal laboratory animals improves neurological function and performance in motor and cognitive tasks, and thus has been proposed as a strategy for treating neurodegenerative diseases. The effects of environmental enrichment have been investigated in the R6/2 mouse model of Huntington’s disease (HD). We and others have shown that providing greater opportunity for social interaction, stimulation, exploration and physical activity improves survival of R6/2 mice. We have also shown previously that HD patients and R6/2 mice suffer from disruptions to their circadian rhythms, which may have a detrimental effect on cognition, general health and survival. In this study, we examined the effects of a daily period of environmental enrichment on the behavioural phenotype and circadian activity of R6/2 mice. Separate groups of mice received either daily exposure to a large playground box (containing running wheels and other toys), or remained in their home cage. These two groups were subdivided into handled (stimulated throughout the experimental period) or non-handled groups. All mice were assessed for survival, body weight, SHIRPA scores and cognitive performance in the Morris water maze (MWM). We found that mice given access to the playgrounds were more active throughout the enrichment period than home cage mice, regardless of genotype or sex. Male R6/2 playground mice had increased lifespan compared to the home cage group, but there was no effect on survival of female R6/2 mice. Handling had beneficial effects on body weight of male R6/2 mice, but a detrimental effect on R6/2 female mice (and no effect on WT mice of either sex). There was no effect of either enrichment or handling on performance of R6/2 mice in the MWM. This study shows that environmental enrichment has varying effects on R6/2 mice depending upon sex and genotype. The causes of these differences have yet to be identified, but may relate to stress responses. Support: CHDI Inc. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Wood NI, Skillings EA, McAllister CJ, Carta V and Morton AJ (2009). Sex and genotype differences in a transgenic mouse model of Huntington's disease in response to environmental enrichment. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.348 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Jun 2009; Published Online: 15 Jun 2009. * Correspondence: Nigel I Wood, University of Cambridge, Department of Pharmacology, Paris, United Kingdom, niw20@cam.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nigel I Wood Elizabeth A Skillings Catherine J McAllister Valentina Carta A. J Morton Google Nigel I Wood Elizabeth A Skillings Catherine J McAllister Valentina Carta A. J Morton Google Scholar Nigel I Wood Elizabeth A Skillings Catherine J McAllister Valentina Carta A. J Morton PubMed Nigel I Wood Elizabeth A Skillings Catherine J McAllister Valentina Carta A. J Morton Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sex differences in the renal handling of protein from high casein and high soy diets in mice

Soy protein diet appears to reduce the rate of chronic kidney disease (CKD) compared to milk protein diet. The purpose of this study was to compare high soy with high casein consumption on protein excretion in mice. The study contained two exact protocols – one with males and one with females. Each protocol began with 25‐day old mice in metabolic cages. One group consumed 40% casein and the other consumed an isocaloric 40% soy diet for 25 days (n=6 per group). Daily measurements included food intake and protein excretion. In both protocols, the casein group excreted more protein (mg/day) than the soy group as measured on the 25th day (males: 22.9±2.5 vs 12.7±.9, p<.009; females: 10.2±1.7 vs 5.4±8, p<.03). Daily urine protein determined via urinalysis strips supported these differences. Females excreted significantly less protein compared to males despite equal protein consumption. We conclude that high soy intake induces less proteinuria compared to high casein. Female mice excrete less protein compared to males either on high soy or high casein. These data support the benefits of soy protein in CKD patients and indicate sex differences in the renal handling of high protein diets.

Strain‐ and Wheel Type‐Dependent Variations in Running Wheel Activity in Mice

Numerous studies have shown positive effects of running wheels on behavioral measures, such as conditioned responding and memory. In the present study, we examined running wheel activity in mice housed under various conditions. Two inbred mouse strains were examined (C57Bl6 and BalbC; 5–7 weeks old). Mice were singly housed under two different conditions. One group was housed in ventilated racks and had access to low‐profile wireless running wheels. The second group was housed in conventional cages and had access to “pet‐store” running wheels. On the first day of wheel access, running levels were similar in BalbC and C57Bl6 mice housed in ventilated racks with low‐profile wheels (4.26±1.11 km vs 4.88±1.31 km, respectively). However, BalbC mice in conventional cages with “pet‐store” wheels ran significantly less than C57Bl6 mice on the first day they had access to wheels (1.67±0.66 km vs. 5.16±1.30 km, p<0.05). Running activity increased over several days in all mice. After 7 days, running levels were similar in BalbC and C57Bl6 mice in both ventilated racks with low‐profile wheels (8.53±1.22 km and 6.17±1.22 km, respectively) and in conventional cages with “pet‐store” wheels (5.42±1.26 km and 7.89±1.15 km, respectively). Mice in different housing conditions run similar levels when given access to wheels having different designs, however strain differences exist.

Procedural learning and cognitive flexibility in a mouse model of restricted, repetitive behaviour

Restricted, repetitive behaviours (e.g., stereotypies, compulsions, rituals) in neurodevelopmental disorders have been linked to alterations in cortico-basal ganglia circuitry. Cognitive processes mediated by this circuitry (e.g., procedural learning, executive function) are likely to be impaired in individuals exhibiting high rates of repetitive behaviour. To test this hypothesis, we assessed both procedural learning and cognitive flexibility (reversal learning) using a T-maze task in deer mice (Peromyscus maniculatus) exhibiting various rates of repetitive behaviour (vertical jumping and backward somersaulting). These mice exhibited high rates of stereotypy when reared in standard rodent cages, and such behaviour was significantly attenuated by housing them in larger more complex environments. Mice reared in complex environments exhibited significantly better procedural and reversal learning than standard caged mice. Thus, early experience associated with the prevention and attenuation of stereotypy was associated with better striatally mediated learning and cognitive flexibility. Stereotypy score was significantly correlated with the number of errors made in reversal learning, and interacted with housing condition to affect overall cognitive performance. Our findings support the applicability of the deer mouse model of spontaneous stereotypy to a wider range of restricted, repetitive behaviour (e.g., insistence on sameness) typical of neurodevelopmental disorders.