RESUMEN
There are growing concerns about the impact of pollution on maternal and infant health. Despite an extensive correlational literature, observational studies which adopt methods that seek to address potential biases due to unmeasured confounders draw mixed conclusions. Using a population database of births in Northern Ireland (NI) linked to localized geographic information on pollution in mothers' postcodes (zipcodes) of residence during pregnancy, we examine whether prenatal exposure to PM2.5 is associated with a comprehensive range of birth outcomes, including placental health. Overall, we find little evidence that particulate matter is related to infant outcomes at the pollution levels experienced in NI, once we implement a mother fixed effects approach that accounts for time-invariant factors. This contrasts with strong associations in models that adjust for observed confounders but without fixed effects. While reducing ambient air pollution remains an urgent public health priority globally, our results imply that further improvements in short-run levels of prenatal PM2.5 exposure in a relatively low-pollution, higher-income country context, are unlikely to impact on birth outcomes at the population level.
Asunto(s)
Contaminación del Aire , Exposición Materna , Material Particulado , Resultado del Embarazo , Humanos , Material Particulado/efectos adversos , Material Particulado/análisis , Femenino , Embarazo , Resultado del Embarazo/epidemiología , Adulto , Recién Nacido , Irlanda del Norte/epidemiología , Contaminación del Aire/efectos adversos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Bases de Datos Factuales , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisisRESUMEN
OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.
RESUMEN
OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.
RESUMEN
OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.
RESUMEN
Anorexia nervosa (AN) is an eating disorder that is thought to emerge through biological predisposition(s) within sociocultural context(s). Practical and ethical concerns limit study of the etiology of this disorder in humans, and in particular the biological aspects. Laboratory animal models have a pivotal role in advancing our understanding of the neurobiological, physiological and behavioral aspects of this disorder, and developing new treatment strategies. One shortcoming of animal models, including activity based anorexia (ABA) in rodents, is that they cannot fully capture the contextual aspects of AN. In this article we discuss the merits of an alternate approach, cost-based anorexia (CBA). CBA is conceptually founded in behavioral economics and its magnitude is influenced by several relevant contextual aspects of feeding.
Asunto(s)
Anorexia Nerviosa/fisiopatología , Modelos Animales de Enfermedad , Animales , Conducta Animal , Humanos , Ratones , Primates , RatasRESUMEN
Intake and body weight were recorded in a closed economy as male and female C57BL/6 mice progressed through either fixed interval (FI) or fixed unit price (FUP) schedules of cost for 20-mg food pellets. Access to food was constrained to four 40 min food opportunities (FOs) per day, spaced 4-h apart through the dark phase. Nose poke responses and pellet deliveries were collected at 10-s resolution to allow pellet-by-pellet analysis. In the FI protocol, mice maintained adequate food intake and body weight through the study, even though at the highest FI (50-s) they spent the entire 40-min FOs engaged in eating at or near the maximum rate allowed by the schedule. In the FUP protocol, mice greatly reduced their intake and lost weight at the highest FUP (50 responses/pellet). The analysis of response and pellet distributions showed these mice were not filling the FOs with responding and ate less at dusk (FO #1) and dawn (FO #4) than at FOs #2 and 3 in the middle of the night. The principal, and unexpected, sex difference was that females tended to eat more than males despite lower body weight, but behavioral changes as a function of feeding cost or schedule were qualitatively similar in both sexes. These results show that slow eating as imposed by an FI is not sufficient to produce hypophagia and, in the FUP protocol, hypophagia cannot be explained by slowed eating due to response requirements. We discuss the role of effort or time in FUP-induced anorexia, and suggest this murine model may emulate some aspects of human anorexia nervosa better than current activity-based protocols.
Asunto(s)
Anorexia/psicología , Ingestión de Alimentos , Conducta Alimentaria , Animales , Conducta Animal , Peso Corporal , Condicionamiento Operante , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Factores SexualesRESUMEN
Rats and mice were studied for changes in meal-taking structure in a closed operant food economy, in which the consummatory or unit prices for food were increased. In experiment 1, as food price increased, male rats modestly decreased the number of meals per day and increased mean meal size. Female rats were similar to males but had smaller meal size and, at low costs, took more meals per day. In experiment 2, male and female B6 mice reduced food intake as price increased, accompanied by decreased meal number without change in meal size. They showed grazing-like behavior in the first part of the night. In contrast, we report in experiment 3, a large increase in intake and meal size during the final trimester of pregnancy. In experiment 4, we report that CD1 male mice subjected to a unit price series performed comparably to rats, and not like B6 mice. Other CD1 mice were tested using an interval schedule, and we found that mice were able to adapt eating patterns to greatly increased time demands without compromising total intake. Data are discussed in terms of the intercalation of food acquisition with global patterns of activity. Such interactions of organism and food environment are in particular need of mechanistic investigation.
Asunto(s)
Condicionamiento Operante , Ingestión de Alimentos , Conducta Alimentaria , Animales , Peso Corporal , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Embarazo , Ratas , Ratas Sprague-Dawley , Factores Sexuales , Especificidad de la Especie , Factores de TiempoRESUMEN
Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (-)-trans-(2S,4R)-4-(3'[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (-)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (-)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (-)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (-)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (-)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (-)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders.
Asunto(s)
2-Naftilamina/análogos & derivados , Antipsicóticos/farmacología , Receptor de Serotonina 5-HT2A/metabolismo , Receptor de Serotonina 5-HT2B/metabolismo , Receptor de Serotonina 5-HT2C/metabolismo , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , 2-Naftilamina/química , 2-Naftilamina/farmacología , Anfetamina/farmacología , Animales , Antipsicóticos/química , Estimulantes del Sistema Nervioso Central/farmacología , Conducta Alimentaria/efectos de los fármacos , Células HEK293 , Humanos , Hipercinesia/tratamiento farmacológico , Hipercinesia/etiología , Masculino , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/etiología , Trastornos Psicóticos/fisiopatología , Ensayo de Unión Radioligante , Agonistas del Receptor de Serotonina 5-HT2/química , Antagonistas del Receptor de Serotonina 5-HT2/química , Estereoisomerismo , Factores de TiempoRESUMEN
RATIONALE: Stable isotope analysis is a valuable technique for dietary estimation in ecological and archaeological research, yet many variables can potentially affect tissue stable isotope signatures. Controlled feeding studies across a range of species have consistently demonstrated impacts of caloric restriction on tissue stable isotope ratios, but most have focused on juvenile, fasting, and/or starving individuals, and most have utilized soft tissues despite the importance of bone for paleodietary analyses. The goal of this study was to determine whether temporally defined, moderate food restriction could affect stable carbon and/or nitrogen isotope ratios in adult mammalian bone - a tissue that arguably reflects long-term dietary signals. METHODS: Adult rats fed a standard laboratory diet were restricted to 45% of ad libitum intakes for 3 or 6 months. Relevant anatomical and physiological parameters were measured to confirm that the restriction protocol resulted in significant nutritional stress and to provide independent data to facilitate interpretation of stable isotope ratios. Femoral bone δ(13)Ccollagen, δ(15)Ncollagen, and δ(13)Capatite values were determined by isotope ratio mass spectrometry. RESULTS: Calorie-restricted animals exhibited a small, yet significant enrichment in (15)Ncollagen compared with control animals, reflecting protein-calorie stress. While the δ(13)Ccollagen values did not differ, the δ(13)Capatite values revealed less enrichment in (13)C than in controls, reflecting catabolism of body fat. Independent anatomical and physiological data from these same individuals support these interpretations. CONCLUSIONS: Results indicate that moderate caloric restriction does not appreciably undermine broad interpretations of dietary signals in adult mammalian bone. Significant variability among individuals or groups, however, is best explained by marked differences in energy intake over variable timescales. An inverse relationship between the δ(13)Capatite and δ(15)Ncollagen values observed in this study indicates that a more robust pattern is expected with more severe or prolonged restriction and suggests this pattern may have utility as a marker of food deprivation in archaeological populations.
Asunto(s)
Huesos/química , Restricción Calórica , Isótopos de Carbono/análisis , Isótopos de Nitrógeno/análisis , Animales , Dieta , Hormonas/sangre , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Particulate matter suspended in the air that is comprised of microscopic particles with a diameter of 2.5µm or less (PM2.5) is among the most impactful pollutants globally. Extensive evidence shows exposure to ambient PM2.5 is associated with a wide range of poor health outcomes. However, few studies examine long-run pollution exposures in nationally representative data. This study exploits Census data for Northern Ireland, linked to average PM2.5 concentrations at the 1x1km grid-square level during the period 2002-2010. We combine outcome measures in 2011 with data on complete residential histories. Before adjusting for other covariates, we show strong relationships between PM2.5 exposure, self-rated general health, disability, and all available (eleven) domain-specific health measures in the data. Associations with poor general health, chronic illness, breathing difficulties, mobility difficulties, and deafness are robust to extensive conditioning and to further analysis designed to examine sensitivity to unobserved confounders.
RESUMEN
The objectives of this paper are to first present physiological and ecological aspects of the unique motivational state of sodium appetite, then to focus on systemic physiology and brain mechanisms. I describe how laboratory protocols have been developed to allow the study of sodium appetite under controlled conditions, and focus on two such conditions specifically. The first of these is the presentation a sodium-deficient diet (SDD) for at least one week, and the second is accelerated sodium loss using SDD for 1-2 days coupled with the diuretic furosemide. The modality of consumption is also considered, ranging from a free intake of high concentration of sodium solution, to sodium-rich food or gels, and to operant protocols. I describe the pivotal role of angiotensin and aldosterone in these appetites and discuss whether the intakes or appetite are matched to the physiological need state. Several brain systems have been identified, most recently and microscopically using molecular biological methods. These include clusters in both the hindbrain and the forebrain. Satiation of sodium appetite is often studied using concentrated sodium solutions, but these can be consumed in apparent excess, and I suggest that future studies of satiation might emulate natural conditions in which excess consumption does not occur, using either SDD only as a stimulus, offering a sodium-rich food for the assessment of appetite, or a simple operant task.
Asunto(s)
Apetito , Sodio en la Dieta , Apetito/fisiología , Sodio , Diuréticos , Furosemida , SaciedadRESUMEN
This collection of outstanding papers is a trove for all concerned with salt intake [...].
Asunto(s)
Apetito , Hambre , Ingestión de Energía , Cloruro de Sodio , Cloruro de Sodio DietéticoRESUMEN
The aim of this study was to examine the effects of a serotonergic anorectic agent, dexnorfenfluramine (DNOR), on food intake in mice whose meals were constrained to specified periods each day and by effort. Mice were forced to adopt a human-like pattern of regular meals by making food available for four periods of 40 min/24-h period, mostly at night. They lived in behavior test chambers with a closed economy for food and were required to emit a fixed unit price (FUP) of either 2 or 25 nose pokes (FUP2, FUP25) to receive a 20 mg pellet of food. Once responding and intake were stable, mice were injected with a vehicle or DNOR (3 or 6 mg/kg) 1 h before a specified feeding opportunity. Food intake was dose-dependently suppressed at the next meal and to a greater extent when the cost of food was high (FUP25). Within a meal, the effect of the drug was the greatest in the first half of the available time. Therefore, the anorectic effect of DNOR was modified by the concurrent cost of food.
Asunto(s)
Depresores del Apetito/farmacología , Conducta Alimentaria/efectos de los fármacos , Comidas , Neuronas/efectos de los fármacos , Norfenfluramina/farmacología , Respuesta de Saciedad/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Animales , Depresores del Apetito/administración & dosificación , Conducta Animal/efectos de los fármacos , Condicionamiento Operante , Relación Dosis-Respuesta a Droga , Ingestión de Energía/efectos de los fármacos , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Receptor de Serotonina 5-HT2C/química , Receptor de Serotonina 5-HT2C/metabolismo , Recompensa , Antagonistas del Receptor de Serotonina 5-HT2/administración & dosificación , Factores de TiempoRESUMEN
Ad libitum feeding patterns in mice show substantial differences between laboratories, in addition to large individual and time-of-day differences. In the present study, we examine how mice work for food when access to food is temporally restricted and so they are forced to take discrete meals. In a first experiment, separate groups of ICR:CD1 mice were given access to food for 4, 8 or 16 opportunities or meals per day, with the duration of access at each opportunity adjusted reciprocally so that the total time of availability was 160 min per day in all three conditions. During the periods of availability, mice were able to earn food pellets by nose poke responses, according to an incrementing series of fixed unit prices (FUP: 2, 5, 10, 25) with each schedule in force for 3-4 days. Total food intake was similar in all three groups, indicating that mice generally were able to adjust their intake to a range of temporal availabilities. In each group, food demand fell as FUP increased. In the 8 and 16 meal groups, no food was eaten in many of the opportunities. Within an opportunity, the rate of intake generally declined with time, indicative of satiation. At low FUPs, later opportunities in each day were associated with smaller meals than earlier opportunities; in contrast, at high FUPs the first opportunity was also a small meal. Collectively, these results show that mice eat less at higher costs but not because of time constraints of the schedule: instead, they exhibit an elective anorexia. In the second experiment, we examined whether snacking between imposed meals would affect subsequent meal(s). Mice were adapted to the foregoing 8 opportunity protocol. Then, half the mice received free snacks of sugar cubes after the 3rd, 4th and 5th meal opportunities and the intakes of sugar and pellets were examined at low and high unit costs for pellets (FUP2 and 25). At FUP2, mice decreased demand for pellets and compensated energetically for the sugar they consumed. At FUP25, mice also decreased demand, but by less than the energy obtained from sugar. These data show that choice for pellets over a free palatable snack, and subsequent compensation of energy intake, is modified by effort and demand.
Asunto(s)
Apetito/fisiología , Conducta Alimentaria/psicología , Saciedad/fisiología , Animales , Condicionamiento Operante , Carbohidratos de la Dieta/análisis , Ingestión de Energía/fisiología , Abastecimiento de Alimentos/economía , Masculino , Ratones , Ratones Endogámicos ICR , Esquema de Refuerzo , Pérdida de Peso/fisiologíaRESUMEN
Mice with homozygous genetic disruption of the melanocortin-4 receptor gene (MC4R-/-) are known to be hyperphagic and become obese, while those with disruption of the melanocortin-3 receptor gene (MC3R-/-) do not become markedly obese. The contribution of MC3R signaling in energy homeostasis remains little studied. In the present work, we compare MC3R-/- mice with wild-type (WT), MC4R-/-, and mice bearing disruption of both genes (double knockout, DKO) on select feeding and neuroanatomical dimensions. DKO mice were significantly more obese than MC4R-/-, whereas MC3R-/- weighed the same as WT. In a food demand protocol, DKO and MC4R-/- were hyperphagic at low unit costs for food, due primarily to increased meal size. However, at higher costs, their intake dropped below that of WT and MC3R-/-, indicating increased elasticity of food demand. To determine whether this higher elasticity was due to either the genotype or to the obese phenotype, the same food demand protocol was conducted in dietary obese C57BL6 mice. They showed similar elasticity to lean mice, suggesting that the effect is of genotypic origin. To assess whether the increased meal size in MC4R-/- and DKO might be due to reduced CCK signaling, we examined the acute anorectic effect of peripherally administered CCK and subsequently the induction of c-Fos immunoreactivity in select brain regions. The anorectic effect of CCK was comparable in MC4R-/-, DKO, and WT, but it was unexpectedly absent in MC3R-/-. CCK-induced c-Fos was lower in the paraventricular nucleus in MC3R-/- than the other genotypes. These data are discussed in terms of demand functions for food intake, MC receptors involved in feeding, and their relation to actions of gut hormones, such as CCK, and to obesity.
Asunto(s)
Ingestión de Alimentos/genética , Melanocortinas/farmacología , Receptor de Melanocortina Tipo 3/genética , Receptor de Melanocortina Tipo 4/genética , Animales , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Melanocortinas/genética , Ratones , Ratones Noqueados , Receptor de Melanocortina Tipo 4/fisiologíaRESUMEN
Dysfunctional feeding behavior has a bidirectional aspect, too little and too much. The former reflects restricted eating and, in extreme, becomes an eating disorder such as anorexia nervosa (AN). The latter reflects lack of restraint and leads to obesity and life-shortening metabolic syndrome. Both of these dysfunctions have proven extremely difficult to prevent or treat, and the use of animal models that have translational validity may be one of the most cost-effective ways of advancing. This chapter describes some of the laboratory protocols using rodents that are available to model human eating dysfunctions.
Asunto(s)
Modelos Animales de Enfermedad , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Alimentación Animal , Animales , Conducta Alimentaria , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Humanos , Ratones , RatasRESUMEN
The exclusion of female rodents from biomedical research is well documented and persists in large part due to perceptions that ovulatory cycles render female traits more variable than those of males, and females must be tested at each of four stages of the estrous cycle to generate reliable data. These beliefs are not empirically based. The magnitude of trait variance associated with the estrous cycle may be sufficiently low and of little impact, or trait variability of males tested on 4 consecutive days may be as great as that of females over the 4 days of the estrous cycle. Here, we analyzed food intake data from mice in 4-day blocks, corresponding to the females' 4-day estrous cycle in several schedules of food procurement or reward. Variance was compared within and across individual mice. In no instance did the overall variance differ by sex under any of the food reward schedules. This extends earlier observations of trait variability in body temperature and locomotor activity of mice and supports the claim that there is no empirical basis for excluding female rodents from biomedical research.
Asunto(s)
Ingestión de Alimentos/fisiología , Ciclo Estral/fisiología , Locomoción/fisiología , Animales , Temperatura Corporal/fisiología , Femenino , Masculino , Ratones , Nariz/fisiología , Ratas , RoedoresRESUMEN
Minimization and alleviation of stress are generally viewed as desirable aspects of laboratory animal management and use. However, achieving that goal requires an unambiguous and valid measure of stress. Glucocorticoid concentrations are commonly used as a physiologic index of stress. Measurement of glucocorticoids in blood, serum or plasma clearly reflects many types of both acute and chronic stress. However, the rapid rise in concentrations of circulating glucocorticoids that occurs even with relatively simple manipulations such as handling has led to the increased use of fecal glucocorticoid metabolite (FCM) assays, which provide a temporally integrated measure that may allow a more accurate interpretation of chronic stressors. In this review, we consider 3 aspects of glucocorticoids as a measure of stress. First, we discuss the analytic and interpretational pitfalls of using FCM concentrations as an index of stress in mice and rats. Second, we consider evidence that some degree of stress may benefit animals by priming physiologic and behavioral adaptations that render the animals more resilient in the face of stress. Finally, we use 2 situations-social housing and food restriction-to illustrate the concept of hormesis-a biologic phenomenon in which a low dose or intensity of a challenge has a beneficial effect, whereas exposure to high doses or intensities is detrimental.
Asunto(s)
Corticosterona/análisis , Ratones , Ratas , Estrés Fisiológico/fisiología , Animales , Biomarcadores/análisis , Heces , Hormesis/fisiologíaRESUMEN
The purpose of this study is to compare the effect of unpredictable (U) or predictable (P) food delivery on health and longevity in mice. From 2 months of age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic diet either ad libitum (AL), or as imposed meals delivered as small pellets at either P or U times, frequencies, or amounts. The total daily food consumed by all groups was the same. The AL group gained body weight faster than either P or U groups, and had ~12% shorter median life span compared with either P or U groups. Bimonthly noninvasive body composition determinations showed that the differences in body weights were due to differences in fat and lean mass. Postmortem examinations revealed that the organ pathologies were similar in all groups, but a larger fraction of P and U mice were euthanized due to end-of-life suffering. There were no systematic differences in outcome measures between P and U groups suggesting that, within the range studied, the temporal pattern of food delivery did not have a significant metabolic effect.
Asunto(s)
Peso Corporal/fisiología , Ingestión de Alimentos/fisiología , Privación de Alimentos/fisiología , Longevidad/fisiología , Animales , Composición Corporal/fisiología , Ingestión de Energía , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Capillary electrophoresis coupled with laser-induced fluorescence detection (CE-LIF) provides 15-s temporal resolution of amino acid levels in microdialysate, which, for the first time, allows almost real time measurement of changes during episodes of behavior. We trained Sprague-Dawley rats to self-administer either 10% ethanol-containing gelatin or non-alcoholic gelatin in a typical operant chamber. After rats reached stable daily levels of responding, microdialysis probes were inserted into nucleus accumbens and samples were collected before, during and after operant sessions with on-line analysis via CE-LIF. During the first 15 min of the operant session, there was a significant increase in taurine that correlated with the amount of ethanol consumed (R(2)=0.81) but no change in rats responding for plain gel. There were large, consistent increases in glycine in both the ethanol and plain gel groups which correlated with the amount of gel consumed. A smaller increase was observed in rats with free non-operant access to plain gel compared to the increase seen with the same amount of gel consumed under operant conditions. When rats were given a time out after each delivery of gel in the operant protocol, the greatest increase of glycine was obtained with the longest time out period. Thus, increases in glycine in nucleus accumbens appear to be related to anticipation of reinforcement.