RESUMEN
Although corticosterone (CORT) regulates many physiological mechanisms, the associations between CORT levels, immunocompetence, energy expenditures and overwinter survival have not been examined. Here, we studied individual variation in CORT level extracted from hair, immunocompetence quantified as the neutrophil-to-lymphocyte (N/L) ratio, total white blood cells (WBC) and natural antibody levels (NAbs), along with the resting (RMR) and peak metabolic rates (PMR) and mortality during three consecutive winter seasons in a natural population of the root vole, Microtus oeconomus. In early winter, hair CORT level was strongly positively associated with body mass and inversely related to voles' ability to survive. We suggest that the observed association between hair CORT level and body mass may be the key component of the physiological nexus driving the survivorship of individual rodents. Additionally, hair CORT was a significant predictor of variation of the whole body RMR, which in turn enhanced overwinter survival in the studied population. On the other hand, hair CORT was not significantly associated with changes in the blood indices. Interestingly, the analysis carried out only during the first year of study (2008), which was characterized by a high population density and prevalence of infestation with a blood protozoan, Babesia spp., showed that the intensity of the infestation was negatively correlated with both the hair CORT level and the N/L ratio. Because CORT is often considered immunosuppressive, we expected a positive association between its level and the N/L ratio. However, hair CORT did not significantly correlate with the N/L ratio. We suggest that the lack of an association between hair CORT and the N/L ratio resulted from a small inter-individual variation in the N/L ratio in 2008, which was much higher and less variable than in the other years of our study.
Asunto(s)
Arvicolinae/inmunología , Arvicolinae/metabolismo , Metabolismo Basal , Corticosterona/metabolismo , Cabello/metabolismo , Inmunocompetencia , Estaciones del Año , Animales , Peso Corporal , Corticosterona/sangre , Femenino , Masculino , Probabilidad , Análisis de SupervivenciaRESUMEN
The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice.
Asunto(s)
Metabolismo Basal/fisiología , Calor , Inmunidad/fisiología , Análisis de Varianza , Animales , Regulación de la Temperatura Corporal/fisiología , Peso Corporal/fisiología , Hemocianinas/inmunología , Inmunidad Humoral , Inmunización , Recuento de Leucocitos , Ganglios Linfáticos/anatomía & histología , Ratones , Especificidad de ÓrganosRESUMEN
Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.
Asunto(s)
Metabolismo Basal/fisiología , Estrés Oxidativo , Reproducción/fisiología , Animales , Metabolismo Basal/genética , Catalasa , Daño del ADN , Femenino , Riñón/enzimología , Hígado/enzimología , RatonesRESUMEN
Experimental manipulation of energy expenditure has long been recognized as an effective means for identifying causative effects and avoiding confounded interpretations arising from spurious correlations. This approach has been successfully applied mainly to studies on birds, particularly on reproducing adults, whereas manipulations in mammals have proved more problematic. Here, we tested the hypothesis that shaving off 50% of the dorsal pelage should effectively increase energy expenditure in wild root voles (Microtus oeconomus) in their natural environment. We measured daily energy expenditure (DEE), using doubly labelled water in shaved and unshaved voles at the beginning of winter. The difference in DEE (corrected for body mass and year effects) between experimental and control group fluctuated from 11.5% to 17.3%. Probability of recapture over the 3 day DEE assay was strongly dependent on body mass, but did not differ between shaved and unshaved animals; however, a prevalence of larger (heavier) shaved individuals was observed. Shaved animals lost more weight between the first and second trapping. Shaving therefore appears to be an effective method of increasing the cost of total DEE in wild endotherms in their natural environment.
Asunto(s)
Arvicolinae/fisiología , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Cabello , Animales , Regulación de la Temperatura Corporal/fisiología , Óxido de Deuterio , Isótopos de OxígenoRESUMEN
Despite its presumed significance, the association between immune defence, energy expenditures and overwinter survival is rarely studied. We analysed individual variation in immunocompetence quantified as neutrophil-to-lymphocyte ratio (N/L), total white blood cells (WBC) and natural antibody levels, along with resting (RMR) and peak metabolic rates (PMR) and mortality during three consecutive winter seasons in a natural population of the root vole, Microtus oeconomus. In early winter, WBC count was negatively correlated with RMR, whereas N/L ratio was negatively correlated with swim-elicited PMR. We suggest that while the first correlation reflected the trade-off between energy allocation in immunocompetence and other metabolically demanding processes, the latter correlation stemmed from stress-induced immunosuppression elicited by the necessity to cope with swimming in frequently flooded habitat. In addition, the analysis carried out during the first year of study characterized by a high population density and prevalence of infestation with a blood parasite--Babesia spp., showed that its intensity was inversely correlated with the N/L ratio. In summary, our results suggest that elevated N/L ratio increases the winter survival of free-ranging rodents by increasing their ability to cope with parasitic infections.
Asunto(s)
Arvicolinae/fisiología , Metabolismo Energético , Inmunocompetencia , Estaciones del Año , Sobrevida , Animales , Arvicolinae/inmunología , Arvicolinae/metabolismoRESUMEN
Dietary restriction (DR)-related delay of ageing is hypothesized to be mediated by the reduction of the metabolic rate (MR). However, studies on the effect of DR on MR have produced equivocal results. We demonstrated that this lack of congruency can be due to a variation in the initial level of MR within a given pool of experimental subjects. We subjected laboratory mice from two line types divergently selected for basal MR (BMR) to 30% DR lasting 6 months to test whether the effect of DR depends on the initial variation in BMR and peak MR. BMR and peak MR were independently affected by DR. The effect of DR was stronger in line types with higher initial levels of MR. Line-type-specific changes in the proportions of body components explained contrasting effects of DR on the mass-corrected BMR, which decreased in the high-BMR line type and did not change in the low-BMR line type. We conclude that the initial variation in MR can significantly affect response to DR. However, we found no association between the level of MR and mechanisms underlying the susceptibility to or protection against oxidative stress.
Asunto(s)
Metabolismo Basal/fisiología , Tamaño Corporal/fisiología , Restricción Calórica , Dieta , Carácter Cuantitativo Heredable , Adiposidad/fisiología , Análisis de Varianza , Animales , Antioxidantes/metabolismo , Temperatura Corporal/fisiología , Peso Corporal/fisiología , Membrana Celular/metabolismo , Ácidos Grasos/metabolismo , Conducta Alimentaria/fisiología , Ratones , Tamaño de los Órganos , Especificidad de Órganos , Fosfolípidos/metabolismo , Suero/metabolismo , Natación/fisiologíaRESUMEN
The basal metabolic rate (BMR) accounts for 60-70% of the daily energy expenditure (DEE) in sedentary humans and at least 50% of the DEE in laboratory mice in the thermoneutral zone. Surprisingly, however, the significance of the variation in the BMR is largely overlooked in translational research using such indices as physical activity level (PAL), i.e., the ratio of DEE/BMR. In particular, it is unclear whether emulation of human PAL in mouse models should be carried out within or below the thermoneutral zone. It is also unclear whether physical activity within the thermoneutral zone is limited by the capacity to dissipate heat generated by exercise and obligatory metabolic processes contributing to BMR. We measured PAL and spontaneous physical activity (SPA) in laboratory mice from two lines, divergently selected towards either high or low level of BMR, and acclimated to 30 °C (i.e., the thermoneutral zone), 23 or 4 °C. The mean PAL did not differ between both lines in the mice acclimated to 30 °C but became significantly higher in the low BMR mouse line at the lower ambient temperatures. Acclimation to 30 °C reduced the mean locomotor activity but did not affect the significant difference observed between the selected lines. We conclude that carrying out experiments within the thermoneutral zone can increase the consistency of translational studies aimed at the emulation of human energetics, without affecting the variation in physical activity correlated with BMR.
Asunto(s)
Aclimatación , Metabolismo Basal , Animales , Metabolismo Basal/fisiología , Calor , RatonesRESUMEN
Proximal mechanisms describing the evolution of high levels of basal metabolic rate (BMR) in endotherms are one of the most intriguing problems of evolutionary physiology. Because BMR mostly reflects metabolic activity of internal organs, evolutionary increase in BMR could have been realized by an increase in relative organ size and/or mass-specific cellular metabolic rate. According to the "membrane pacemaker" theory of metabolism, the latter is mediated by an increase in the average number of double bonds (unsaturation index) in cell membrane fatty acids. To test this, we investigated the effect of divergent artificial selection for body-mass-corrected BMR on the mass of internal organs and the fatty acid composition of cell membranes in laboratory mice (Mus musculus). Mice from the high-BMR line had considerably larger liver, kidneys, heart, and intestines. In contrast, the unsaturation index of liver cell membranes was significantly higher in low-BMR mice, mainly because of the significantly higher content of highly polyunsaturated 22 : 6 docosahexanoic fatty acid. Thus, divergent selection for BMR did not affect fatty acyl composition of liver and kidney phospholipids in the direction predicted by the membrane pacemaker theory. We conclude that an intraspecific increase in BMR may rapidly evolve mainly as a result of the changes in size of internal organs, without simultaneous increase of the unsaturation index in cell membrane lipids.
Asunto(s)
Metabolismo Basal/fisiología , Ratones/fisiología , Animales , Animales de Laboratorio , Tamaño Corporal/fisiología , Cruzamiento , Femenino , Corazón/anatomía & histología , Intestino Delgado/anatomía & histología , Intestino Delgado/metabolismo , Riñón/anatomía & histología , Riñón/metabolismo , Hígado/anatomía & histología , Hígado/metabolismo , Masculino , Lípidos de la Membrana/metabolismo , Ratones/anatomía & histología , Ratones/genética , Ratones/metabolismo , Miocardio/metabolismo , Tamaño de los Órganos/fisiologíaRESUMEN
The tools enabling brief assessment of folate intake may be of great value for public health purposes. The aim of the presented study was to design a brief folate-specific food frequency questionnaire for Central and Eastern European population of women, as well as to assess the validity and reproducibility of the designed Folate-Intake Calculation-Food Frequency Questionnaire (Fol-IC-FFQ) on a group of Polish women aged 20-30 years. Participants collected 3-day dietary records and completed the Fol-IC-FFQ twice (FFQ1: directly after the dietary record; and FFQ2: six weeks later). The analysis included an assessment of validity (comparison of the results of FFQ1 and 3-day dietary record) and of reproducibility (comparison of the results of FFQ1 and FFQ2). In assessment of validity, a Bland-Altman index of 5.3% was observed. In assessment of reproducibility, a Bland-Altman index of 2.7% was observed, the share of individuals classified into the same intake adequacy category was over 85%, the share of individuals classified into the same tertile was almost 75%, the weighted κ statistic indicated substantial agreement (0.67) and correlation was significant (p = 0.0000; R = 0.7995). Assessment of the Fol-IC-FFQ revealed a satisfactory level of validity and very good level of reproducibility in the population of young Polish women. The Fol-IC-FFQ may be considered a valid tool for the assessment of folate intake in young Polish women and a promising tool for the assessment of folate intake in young women in Central and Eastern Europe.
Asunto(s)
Registros de Dieta , Encuestas sobre Dietas , Ácido Fólico , Encuestas y Cuestionarios , Adulto , Femenino , Humanos , Estado Nutricional , Polonia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR.
Asunto(s)
Metabolismo Basal/fisiología , Peso Corporal/fisiología , Restricción Calórica/métodos , Condicionamiento Físico Animal/fisiología , Análisis de Varianza , Animales , Índice de Masa Corporal , RatonesRESUMEN
This study was undertaken to examine the trade-off between the cost of thermoregulation and immune function in laboratory mice. Mice were maintained either at 23 degrees C or cold exposed at 5 degrees C for 10 days. Then, they were immunized with sheep red blood cells. Thus, the cold-exposed mice had either experienced or not experienced cold stress prior to immunization. Cold stress elicited a substantial increase in food intake, accompanied by a significant reduction in food digestibility. An increase in mass of metabolically active internal organs (small intestines, heart and kidney) was observed in cold-exposed mice. These findings reassured us that costs of increased thermoregulation caused by cold stress were substantial. The immune response of mice exposed to long-lasting cold stress was significantly lower, but immune response was not affected in short-exposed mice. Differences in immune response between experimental groups accompanied changes in mass of immunocompetent organs (thymus and spleen). Our findings indicate that studies of trade-offs should account for the fact that resource reallocation in response to an environmental challenge may not be immediate. In fact, resource reallocation may be postponed until the new environmental state becomes permanent or until an organism attains physiological adaptation to the current conditions.
Asunto(s)
Frío , Estrés Fisiológico/inmunología , Animales , Animales de Laboratorio , Anticuerpos/inmunología , Peso Corporal , Eritrocitos/inmunología , Conducta Alimentaria , Masculino , Ratones , Tamaño de los Órganos , OvinosRESUMEN
To study whether mounting an immune response is energetically costly, mice from two lines divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate (BMR) were immunized with sheep red blood cells. Their energy budgets were then additionally burdened by sudden transfer from an ambient temperature of 23 degrees C to 5 degrees C. We found that the immune response of H-BMR mice was lower than that of L-BMR mice. However, the interaction between line affiliation and ambient temperature was not significant and cold exposure did not result in immunosuppression in either line. At 23 degrees C the animals of both lines seemed to cover the costs of immune response by increasing food consumption and digestive efficiency. This was not observed at 5 degrees C, so these costs must have been covered at the expense of other components of the energy budget. Cold exposure itself elicited a considerable increase in food intake and the mass of internal organs, which were also heavier in H-BMR than in L-BMR mice. However, irrespective of the temperature or line affiliation, immunized mice had smaller intestines, while cold-exposed immunized mice had smaller hearts. Furthermore, the observed larger mass of the liver and kidneys in immunized mice of both lines kept at 23 degrees C was not observed at 5 degrees C. Hence, immunization compromised upregulation of the function of metabolically active internal organs, essential for meeting the energetic demands of cold. We conclude that the difficulties with a straightforward demonstration of the energetic costs of immune responses in these animals stem from the extreme flexibility of their energy budgets.
Asunto(s)
Metabolismo Basal/fisiología , Frío , Terapia de Inmunosupresión , Ratones/inmunología , Estrés Fisiológico/inmunología , Animales , Constitución Corporal/fisiología , Metabolismo Energético/fisiología , Ratones/metabolismo , Ratones/fisiologíaRESUMEN
The aerobic capacity model postulates that high basal metabolic rates (BMR) associated with endothermy evolved as a correlated response to the selection on maximum, peak metabolic rate Vo2max. Furthermore, the model assumes that BMR and Vo2max are causally linked, and therefore, evolutionary changes in their levels cannot occur independently. To test this, we compared metabolic and anatomical correlates of selection for high and low body mass-corrected BMR in males of laboratory mice of F18 and F19 selected generations. Divergent selection resulted in between-line difference in BMR equivalent to 2.3 phenotypic standard deviation units. Vo2max elicited by forced swimming in 20 degrees C water was higher in the low BMR than high BMR line and did not differ between the lines when elicited by exposure to heliox at -2.5 degrees C. Moreover, the magnitude of swim- and heliox-induced hypothermia was significantly smaller in low BMR mice, whereas their interscapular brown adipose tissue was larger than in high BMR mice. Our results are therefore at variance with the predictions of aerobic capacity model. The selection also resulted in correlated response in food consumption (C) and masses of metabolically active internal organs: kidneys, liver, small intestine, and heart, which fuel maximum, sustained metabolic rate (SusMR) rather than Vo2max. These correlated responses were strong enough to claim the existence of positive, genetic correlations between BMR and the mass of viscera as well as C. Thus, our findings support the suggestion that BMR evolved as a correlated response to selection for SusMR, not Vo2max. In functional terms BMR should therefore be interpreted as a measure of energetic costs of maintenance of metabolic machinery necessary to sustain high levels of energy assimilation rate.
Asunto(s)
Adaptación Fisiológica/genética , Metabolismo Basal/genética , Metabolismo Basal/fisiología , Termogénesis/genética , Termogénesis/fisiología , Animales , Composición Corporal/genética , Peso Corporal/genética , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Conducta Alimentaria/fisiología , Corazón , Intestino Delgado , Riñón , Hígado , Masculino , Ratones , Tamaño de los Órganos/genética , Tamaño de los Órganos/fisiología , Consumo de OxígenoRESUMEN
In many species, dominance increases a male's mating success via intrasexual competition and/or female choice. The level of androgen hormones, mainly testosterone (T), the intensity of scent marking and body mass are traits that are known to be linked to mammalian male social rank. Recently, however, it has been noted that this link between male dominance and the aforementioned traits in natural free-living populations is not universal and does not exist in some species. That is why we tested the hypothesis of whether a male's social rank is related to the expression of T, scent-marking and his body mass. We conducted the study on the promiscuous rodent species, root voles (Microtus oeconomus), which originated from a natural population (wild-born). These tests provided support for the following conclusions: (1) the social status of a male root vole is partly related to his level of testosterone; (2) the highest T level was observed in subdominant males; (3) T levels proved to be independent of male body mass; (4) marking frequency was not dependent on a male's social status nor their body mass; and (5) the mean body mass of dominant, subdominant and subordinate individuals was similar. Our results indicate that in natural free-living populations, the link between the T levels and dominance behaviour of root vole males is ambiguous. Moreover, there is no link between the social status and the intensity of scent-marking. We therefore conclude that in this species, male marking intensity cannot be used as an indicator of social rank.
Asunto(s)
Arvicolinae/fisiología , Dominación-Subordinación , Territorialidad , Testosterona/fisiología , Animales , Arvicolinae/psicología , Tamaño Corporal/fisiología , Masculino , Testosterona/sangreRESUMEN
Basal metabolic rate (BMR) provides a widely accepted benchmark of metabolic expenditure for endotherms under laboratory and natural conditions. While most studies examining BMR have concentrated on inter-specific variation, relatively less attention has been paid to the determinants of within-species variation. Even fewer studies have analysed the determinants of within-species BMR variation corrected for the strong influence of body mass by appropriate means (e.g. ANCOVA). Here, we review recent advancements in studies on the quantitative genetics of BMR and organ mass variation, along with their molecular genetics. Next, we decompose BMR variation at the organ, tissue and molecular level. We conclude that within-species variation in BMR and its components have a clear genetic signature, and are functionally linked to key metabolic process at all levels of biological organization. We highlight the need to integrate molecular genetics with conventional metabolic field studies to reveal the adaptive significance of metabolic variation. Since comparing gene expressions inter-specifically is problematic, within-species studies are more likely to inform us about the genetic underpinnings of BMR. We also urge for better integration of animal and medical research on BMR; the latter is quickly advancing thanks to the application of imaging technologies and 'omics' studies. We also suggest that much insight on the biochemical and molecular underpinnings of BMR variation can be gained from integrating studies on the mammalian target of rapamycin (mTOR), which appears to be the major regulatory pathway influencing the key molecular components of BMR.
Asunto(s)
Animales de Laboratorio/metabolismo , Animales Salvajes/metabolismo , Metabolismo Basal , Animales , Animales de Laboratorio/crecimiento & desarrollo , Animales Salvajes/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica , Humanos , Tamaño de los Órganos , Especificidad de Órganos , Roedores/crecimiento & desarrollo , Roedores/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca(+) (+) ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker - paxilline (10 µM) - irreversibly decreased the non-inactivating K(+) current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K(+) currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K(+) channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca(+) (+) concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K(+) channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC pyramidal neurons of adolescent rats compared with those in the neurons of young and adult rats while their properties did not change across ages.
RESUMEN
To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.
Asunto(s)
Privación de Alimentos/fisiología , Hemocianinas/administración & dosificación , Ratones/inmunología , Ratones/metabolismo , Animales , Animales de Laboratorio , Metabolismo Basal , Peso Corporal/fisiología , Inmunoglobulina M/sangre , Análisis de los Mínimos Cuadrados , Recuento de Leucocitos/veterinaria , Masculino , Tamaño de los Órganos/fisiología , Distribución Aleatoria , Selección GenéticaRESUMEN
Impaired working memory is a common feature of neuropsychiatric disorders. It is dependent on control of the medial prefrontal cortex (mPFC) neurons by dopamine. The purpose of this study was to test the effects of a D1/5-type dopamine receptor agonist (SKF 38393, 10 microM) on the membrane potential and on voltage-dependent fast-inactivating Na+ currents in mPFC pyramidal neurons obtained from adult (9-week-old) rats. Treatment of the pyramidal neurons with SKF 38393 did not affect the membrane potential recorded with the perforated-patch method. When recordings were performed in cellattached configuration, the application of SKF 38393 did not change the Na+ current amplitude and shifted the currentvoltage relationship of the Na+ currents towards hyperpolarisation, thus resulting in an increase of the current amplitudes in response to suprathreshold depolarisations. Pretreatment of the cells with a D1/5 receptor antagonist (SCH 23390, 10 microM) abolished the effect of the D1/5-type receptors on Na+ currents. The effect of the D1/5 agonist was replicated by treating the cells with a membrane-permeable analogue, cAMP (8-bromo-cAMP, 100 microM), and the effect was blocked by treating the cells with a protein kinase A inhibitor, (H-89, 2 microM). In recordings performed from mechanically and enzymatically dispersed pyramidal neurons in the whole-cell configuration, when the cell interior was dialysed with pipette solution, application of the D1/5 agonist decreased the Na+ current amplitude without changing the current-voltage relationship. We conclude that in the mPFC pyramidal neurons in slices with an intact intracellular environment (recordings in the cell-attached configuration), the activation of D1/5 dopamine receptors increases the fast-inactivating Na+ current availability in response to suprathreshold depolarisations. The maximum Na+ current amplitude was not changed. A cAMP/protein kinase A pathway was responsible for the signal transduction from the D1/5 dopamine receptors to the Na+ channels.
Asunto(s)
Corteza Prefrontal/citología , Células Piramidales/fisiología , Receptores Dopaminérgicos/metabolismo , Canales de Sodio Activados por Voltaje/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Fenómenos Biofísicos/efectos de los fármacos , Fenómenos Biofísicos/fisiología , Células Cultivadas , Dopaminérgicos/farmacología , Estimulación Eléctrica , Técnicas In Vitro , Masculino , Técnicas de Placa-Clamp , Células Piramidales/efectos de los fármacos , Ratas , Bloqueadores de los Canales de Sodio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
Theoretical considerations suggest that one of the main factors determining phenotypic flexibility of the digestive system is the size (mass) of internal organs. To test this, we used mice from two lines selected for high and low levels of basal metabolic rate (BMR). Mice with higher BMRs also have larger internal organs and higher daily food consumption (C) under non-stressful conditions. We exposed animals from both lines to a sudden cold exposure by transferring them (without prior acclimation) from an ambient temperature of 23 degrees C to 5 degrees C. Cold exposure elicited a twofold increase in C and a 25% reduction of apparent digestive efficiency. For the same body mass-corrected C, small intestine, kidneys, heart and liver of cold-exposed low-BMR mice were smaller than those of the high-BMR line. Therefore, the internal organs of low-BMR animals were burdened with substantially higher metabolic loads (defined as C or digestible food intake per total mass of a particular organ). The mass-specific activity of citrate synthase (CS) in the liver and kidneys (but not heart) was also lower in the low-BMR mice. The magnitude of phenotypic flexibility of internal organ size and CS activity was strictly proportional to the organ mass (in the case of kidneys and liver, also mass-specific CS activity) prior to an increased energy demand. Thus, phenotypic flexibility had additive rather than multiplicative dynamics. Our results also suggest that variation in BMR positively correlates with the magnitude of an immediate spare capacity that fuels the initial response of internal organs to a sudden metabolic stress.
Asunto(s)
Adaptación Fisiológica/genética , Metabolismo Basal/genética , Animales , Citrato (si)-Sintasa/metabolismo , Frío , Conducta Alimentaria/fisiología , Corazón/anatomía & histología , Corazón/fisiología , Intestino Delgado/anatomía & histología , Intestino Delgado/fisiología , Riñón/anatomía & histología , Riñón/fisiología , Hígado/anatomía & histología , Hígado/fisiología , Ratones , Tamaño de los ÓrganosRESUMEN
Artificial selection experiments are potentially powerful, yet under-utilized tool of evolutionary and physiological ecology. Here we analyze and review three important aspects of such experiments. First, we consider the effects of instrumental measurement errors and random fluctuations of body mass on the total phenotypic variation. We illustrate this with the analysis of measurements of oxygen consumption in an open-flow respirometry set-ups. We conclude that measurement errors and fluctuations of body mass are likely to reduce the repeatability of oxygen consumption by about one third. Using published estimates of repeatability of metabolic rates we also showed that it does not tend to decline with increasing time between measurements. Second, we review data on narrow sense heritability (h(2)) of metabolic rates in mammals. The results are equivocal: many studies report very low (â¼0.1) h(2), whereas some recent studies (including our own estimates of h(2) in laboratory mice, obtained by means of parent-offspring regression) report significant h(2) ≥ 0.4. Finally, we discuss consequences of the lack of replicated lines in artificial selection experiments. We focus on the confounding effect of genetic drift on statistical inferences related to primary (selected) and secondary (correlated) traits, in the absence of replications. We review literature data and analyze them following the guidelines formulated by Henderson (1989, 1997). We conclude that most results obtained in unreplicated experiments are probably robust enough to ascribe them to the effect of selection, rather than genetic drift. However, Henderson's guidelines by no means should be treated as a legitimate substitute of the analysis of variance, based on replicated lines.