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Bradykinin is a well-studied bioactive peptide associated with several physiological functions, including vasodilation and inflammation, in mammals. However, its avian homolog, ornithokinin, has received less research attention in birds. Therefore this study aimed to investigate the effect of intraperitoneal (IP) and intracerebroventricular (ICV) injections of ornithokinin on feeding behavior, cloacal temperature, voluntary activity, crop emptying rate, and blood constituents in chicks (Gallus gallus). We also investigated the effect of lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, on ornithokinin-associated gene expression was also investigated to determine whether activation of the ornithokinin system is induced by bacterial infection. Both IP and ICV injections of ornithokinin significantly decreased feed intake, cloacal temperature, voluntary activity, and crop emptying rate in chicks, but they did not affect the plasma concentration of corticosterone. Additionally, LPS significantly increased the expression of ornithokinin B2 receptor mRNA in several organs. Hence, ornithokinin is associated with a range of physiological responses in chicks and may be related to their response to bacterial infection.
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Galinhas , Corticosterona , Animais , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Galinhas/fisiologia , Ingestão de Alimentos , Comportamento Alimentar , Injeções Intraventriculares , Lipopolissacarídeos/farmacologia , Mamíferos , RNA Mensageiro , TemperaturaRESUMO
Obesity due to high calorie intake induces cardiac hypertrophy and dysfunction, thus contributing to cardiovascular morbidity and mortality. Recent studies in aging suggest that oral supplementation with the natural polyamine spermidine has a cardioprotective effect. Here, the hypothesis was tested that spermidine or voluntary activity alone or in combination protect the heart from adverse effects induced by obesity. Therefore, C57Bl/6 mice (n = 8-10 per group) were subjected to control or high fat diet (HFD) and were left untreated, or either received spermidine via drinking water or were voluntarily active or both. After 30 weeks, the mice were killed and the left ventricle of the hearts was processed for light and electron microscopy. Design-based stereology was used to estimate parameters of hypertrophy, fibrosis, and lipid accumulation. HFD induced cardiac hypertrophy as demonstrated by higher volumes of the left ventricle, cardiomyocytes, interstitium, myofibrils and cardiomyocyte mitochondria. These changes were not influenced by spermidine or voluntary activity. HFD also induced myocardial fibrosis and accumulation of lipid droplets within cardiomyocytes. These HFD effects were enhanced in spermidine treated animals but not in voluntarily active mice. This was even the case in voluntarily active mice that received spermidine. In conclusion, the data confirm the induction of left ventricular hypertrophy by high-fat diet and suggest that-under high fat diet-spermidine enhances cardiomyocyte lipid accumulation and interstitial fibrosis which is counteracted by voluntary activity.
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Cardiomegalia/metabolismo , Fibrose/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Gotículas Lipídicas/metabolismo , Miócitos Cardíacos/metabolismo , Obesidade/metabolismo , Administração Oral , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Dieta Hiperlipídica/efeitos adversos , Fibrose/induzido quimicamente , Fibrose/patologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/patologia , Gotículas Lipídicas/patologia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Miócitos Cardíacos/patologia , Obesidade/induzido quimicamente , Obesidade/patologia , Espermidina/administração & dosagemRESUMO
1. The purpose of the present study was to determine if an intraperitoneal injection of two toll-like receptor-7 (TLR7) agonists, imiquimod and resiquimod, affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate, plasma corticosterone (CORT) and glucose concentrations, and splenic gene expression of cytokines in chicks (Gallus gallus). 2. Although intraperitoneal injection of 100 µg imiquimod significantly increased splenic gene expression of interleukin-1ß (IL-1ß), IL-6, IL-8, and interferon-γ (IFN-γ), it did not affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate or plasma constituents. 3. Intraperitoneal injection of 100 µg resiquimod significantly decreased feed intake, voluntary activity, cloacal temperature, crop-emptying rate and increased plasma corticosterone concentrations. 4. Intraperitoneal injection of resiquimod significantly increased splenic gene expression of IL-1ß, IL-6, IL-8, IFN-γ, and tumour necrosis factor-like cytokine 1A. 5. The results showed that activation of TLR7 is associated with anorexia, hypoactivity, hypothermia, disturbance of feed passage in the digestive tract and the response to stress in chicks.
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Galinhas , Comportamento Alimentar , Receptor 7 Toll-Like , Animais , Cloaca , TemperaturaRESUMO
1. The purpose of the present study was to determine if intracerebroventricular (ICV) and intraperitoneal (IP) injection of polyinosinic-polycytidylic acid (poly I:C), a viral mimetic that binds to toll-like receptor-3 (TLR3), affects food intake, voluntary activity, cloacal temperature, plasma corticosterone (CORT) and glucose concentrations, and crop emptying rate in chicks (Gallus gallus). 2. Both ICV and IP injection of poly I:C significantly decreased food intake. 3. IP but not ICV injection of poly I:C significantly suppressed voluntary activity, whereas ICV injection decreased time spent sitting. Both ICV and IP injection of poly I:C significantly increased plasma CORT and glucose concentration. Neither ICV nor IP injection of poly I:C significantly affected cloacal temperature. 4. In addition, ICV injection of poly I:C significantly reduced crop emptying rate, whereas IP injection had no effect. 5. These results suggested that central TLR3 is related to anorexia, stress response and retardation of crop emptying while peripheral TLR3 is related to anorexia, change in behaviour and stress responses during viral infection in chicks.
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Galinhas/fisiologia , Corticosterona/sangue , Comportamento Alimentar/efeitos dos fármacos , Glucose/metabolismo , Locomoção/efeitos dos fármacos , Poli I-C/administração & dosagem , Animais , Cloaca/efeitos dos fármacos , Cloaca/fisiologia , Papo das Aves/efeitos dos fármacos , Papo das Aves/fisiologia , Digestão/efeitos dos fármacos , Injeções Intraperitoneais/veterinária , Injeções Intraventriculares/veterinária , Masculino , TemperaturaRESUMO
BACKGROUND: The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. METHODS: Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. RESULTS: Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. CONCLUSIONS: These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.
Assuntos
Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Transtornos de Enxaqueca/diagnóstico , Corrida/fisiologia , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Sumatriptana/farmacologia , Animais , Feminino , Isotiocianatos/administração & dosagem , Isotiocianatos/farmacologia , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Sumatriptana/administração & dosagemRESUMO
INTRODUCTION: The effects of voluntary activity initiated in adult mdx (C57BL/10ScSc-DMD(mdx) /J) mice on skeletal and cardiac muscle function have not been studied extensively. METHODS: We studied the effects of 3 months of voluntary wheel running initiated at age 7 months on hindlimb muscle weakness, increased susceptibility to muscle contraction-induced injury, and left ventricular function in mdx mice. RESULTS: We found that voluntary wheel running did not worsen the deficit in force-generating capacity and the force drop after lengthening contractions in either mdx mouse gender. It increased the absolute maximal force of skeletal muscle in female mdx mice. Moreover, it did not affect left ventricular function, structural heart dimensions, cardiac gene expression of inflammation, fibrosis, or remodeling markers. CONCLUSION: These results indicate that voluntary activity initiated at age 7 months had no detrimental effects on skeletal or cardiac muscles in either mdx mouse gender.
Assuntos
Membro Posterior/fisiologia , Miocárdio , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Fatores Etários , Animais , Feminino , Coração/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Atividade Motora/fisiologia , Contração Muscular/fisiologiaRESUMO
OBJECTIVES: Homonegativity adversely affects the health and well-being of homosexuals in society, making it vital to identify factors associated with it. This study investigates whether active membership in voluntary organizations correlates with homonegativity, examining how this varies by gender and age. METHODS: Using the World Values Survey data (2017-2022) from 87,777 participants in 63 countries, we performed binary logistic regression to assess relationships between homonegativity and factors including socioeconomic status, demographics, and voluntary activity participation. RESULTS: Our findings suggest that active membership in certain voluntary organizations correlates with homonegativity levels among both men and women across various age groups. Specifically, active participation in sports or recreational organizations, professional associations, art, music, or educational organizations, and humanitarian or charitable organizations was found to be negatively correlated with homonegativity in specific gender-age groups, albeit with varying degrees of association strength. CONCLUSION: This study highlights the complex relationship between engagement in voluntary organizations and attitudes toward homosexuality, with significant differences observed across gender and age. While identifying a correlation rather than causation, this study suggests the importance of societal and community participation in fostering more tolerant views toward homosexuals. Furthermore, our analysis indicates that demographic and socioeconomic variables, the political freedom of the respondent's country, and the respondent's life satisfaction are also linked to homonegativity.
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PEGPH20, a human recombinant hyaluronidase, has been proposed as a coadjutant to pancreatic cancer chemotherapy. In early trials, patients reported increased widespread muscle pain as the main adverse reaction to PEGPH20. To understand how PEGPH20 caused musculoskeletal pain, we systemically administered PEGPH20 to male mice and measured voluntary wheel activity and pain-related behaviors. These were paired with ex vivo electrophysiology of primary sensory neurons, whole DRG real-time PCR, and immunohistochemistry of hindpaw muscle. PEGPH20 induced significantly lower wheel running, compared with vehicle-treated animals, and decreased mechanical withdrawal thresholds 5 d after PEGPH20 injections. Chemo-sensory muscle afferents showed increased responses to noxious chemical stimulation of their receptive fields (RFs) in the PEGPH20-treated group. This was correlated with upregulation of the NGF receptor TrkA, the transient receptor potential vanilloid type 1 (TRPV1) channel and ATP-sensitive channel P2X3 in the DRG. Immunohistochemistry of hindpaw muscles revealed damage to the muscle architecture and extensive infiltration of the tissue by cells of the myelomonocytic lineage 3 d after PEGPH20 injection. Peripheral macrophage ablation in macrophage Fas-induced apoptosis (MaFIA) mice, however, did not prevent the decreased voluntary activity and instead caused even lower levels of running. These results suggest that disruption of hyaluronic acid (HA) within the muscle extracellular matrix (ECM) sensitizes chemo-nociceptive muscle afferents possibly leading to altered pain-like behaviors. Ablation experiments suggest macrophages are necessary for adequate recovery of voluntary activity after HA disruption. These data support a role for HA and macrophages in tissue integrity and muscle pain development in patients taking PEGPH20.
Assuntos
Ácido Hialurônico , Neoplasias Pancreáticas , Animais , Gânglios Espinais/fisiologia , Humanos , Ácido Hialurônico/uso terapêutico , Masculino , Camundongos , Atividade Motora , Músculo Esquelético , Mialgia , Neoplasias Pancreáticas/tratamento farmacológicoRESUMO
Nitric oxide (NO) is a well-known gaseous signaling molecule that is involved in a variety of physiological and pathological processes in vertebrates. The role of NO in physiological responses of birds has been investigated primarily using NOS inhibitors. Therefore, the effect of the absence of NO is well characterized. However, there is little knowledge on the effects of abundant NO in birds, which is the case in birds that have infections. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) and intracerebroventricular (ICV) injections of sodium nitroprusside (SNP), a NO donor, affected feed intake, voluntary activity, cloacal temperature, crop emptying rate, and blood constituents in domesticated chicks (Gallus gallus) as model birds. We found that both IP and ICV injections of SNP significantly decreased feed intake while there was little effect on voluntary activity. Cloacal temperature was temporarily, but significantly, decreased by both types of injection of SNP. Additionally, both IP and ICV injections of SNP significantly decreased the crop emptying rate. The IP injection of SNP significantly increased the plasma concentrations of NO2/NO3, which are metabolites of NO, and corticosterone, and decreased the plasma glucose concentrations, while the ICV injection had no effect. The IP injection of SNP also showed the tendency to increase the nitrotyrosine level, to increase superoxide dismutase activity, and to decrease catalase activity in the plasma. These results suggest that under specific situations which produce abundant NO such as infection, NO would induce anorexia, hypothermia, inhibition of feed passage, and activation of the hypothalamus-pituitary-adrenal axis in chicks.
Assuntos
Galinhas , Comportamento Alimentar , Animais , Galinhas/fisiologia , Ingestão de Alimentos , Injeções Intraventriculares , Nitroprussiato/farmacologia , TemperaturaRESUMO
Participation in repetitive endurance training decreases sled dogs' voluntary activity and locomotive behaviours; however, the changes in their voluntary physical activity over consecutive rest days has not been examined to assess exercise-recovery. The objective of this study was to examine the changes in behaviour and voluntary activity of sled dogs throughout repetitive incremental conditioning and intermittent rest days. Fourteen dogs (6 males, 8 females; age 3.7 ± 2.7 years; BW 21.5 ± 2.8 kg) underwent 10 weeks of conditioning. Once a week, 5-min video recordings were taken pre- and post-exercise to measure the time spent performing agonistic behaviours, chewing on the gangline, digging, jumping, lunging, posture changing, sitting, standing and lying. Additionally, voluntary physical activity was measured on a day with an exercise bout during baseline, week 4, 5 and 7 and two consecutive rest days during baseline, week 1, 4, 5 and 7. A repeated-measures mixed model was used to analyse data in SAS (v 9.4.). As dogs progressed through their conditioning, the time spent changing posture prior to an exercise bout decreased (p < 0.05), suggesting that dogs may reduce their voluntary locomotive behaviours with increasing exercise. Additionally, dogs were more active during the second consecutive rest day than the first (p < 0.05), suggesting that rest days may provide a short-term recovery period.
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AIM: Exercise is cardioprotective, though optimal interventions are unclear. We assessed duration dependent effects of exercise on myocardial ischemia-reperfusion (I-R) injury, kinase signaling and gene expression. METHODS: Responses to brief (2 day; 2EX), intermediate (7 and 14 day; 7EX and 14EX) and extended (28 day; 28EX) voluntary wheel running (VWR) were studied in male C57Bl/6 mice. Cardiac function, I-R tolerance and survival kinase signaling were assessed in perfused hearts. KEY FINDINGS: Mice progressively increased running distances and intensity, from 2.4 ± 0.2 km/day (0.55 ± 0.04 m/s) at 2-days to 10.6 ± 0.4 km/day (0.72 ± 0.06 m/s) after 28-days. Myocardial mass and contractility were modified at 14-28 days VWR. Cardioprotection was not 'dose-dependent', with I-R tolerance enhanced within 7 days and not further improved with greater VWR duration, volume or intensity. Protection was associated with AKT, ERK1/2 and GSK3ß phosphorylation, with phospho-AMPK selectively enhanced with brief VWR. Gene expression was duration-dependent: 7 day VWR up-regulated glycolytic (Pfkm) and down-regulated maladaptive remodeling (Mmp2) genes; 28 day VWR up-regulated caveolar (Cav3), mitochondrial biogenesis (Ppargc1a, Sirt3) and titin (Ttn) genes. Interestingly, I-R tolerance in 2EX/2SED groups improved vs. groups subjected to longer sedentariness, suggesting transient protection on transition to housing with running wheels. SIGNIFICANCE: Cardioprotection is induced with as little as 7 days VWR, yet not enhanced with further or faster running. This protection is linked to survival kinase phospho-regulation (particularly AKT and ERK1/2), with glycolytic, mitochondrial, caveolar and myofibrillar gene changes potentially contributing. Intriguingly, environmental enrichment may also protect via similar kinase regulation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Isquemia Miocárdica/prevenção & controle , Condicionamento Físico Animal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Glicogênio Sintase Quinase 3 beta/genética , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genéticaRESUMO
Flagellin (Flg) is a globular protein, found in bacterial flagella, that serves as a pathogen-associated molecular pattern and also serves as a toll-like receptor-5 (TLR5) ligand in vertebrates. Most ligands for TLRs are involved in non-specific effects such as anorexia and hypoactivity in an animal infected by bacteria. However, there is little knowledge on the effects of Flg in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of Flg affects food intake, voluntary activity, cloacal temperature, crop emptying rate, blood constituents, and splenic gene expression of cytokines in chicks (Gallus gallus). The effect of Flg22, an N-terminus fragment of Flg, was also investigated. IP injection of 10 µg Flg significantly increased the splenic gene expression of interleukin-8, interferon-γ (IFN-γ), and tumor necrosis factor-like cytokine-1A, suggesting that Flg activated the innate immune system in chicks. The injection of Flg significantly decreased food intake, voluntary activity, blood glucose concentration, and crop emptying rate, and increased cloacal temperature and plasma concentrations of nitrite, nitrate, and corticosterone. However, the injection of Flg22 only affected the splenic gene expression of IFN-γ, indicating that the full-length of Flg is required for its action. These results suggest that Flg, a ligand for TLR5, is related to non-specific symptoms including anorexia, hypoactivity, increase in body temperature, disturbance of food passage in the digestive tract, and the activation of hypothalamic-pituitary-adrenal axis during bacterial infection in chicks.
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Galinhas , Flagelina , Animais , Comportamento Alimentar , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-SuprarrenalRESUMO
Physical inactivity is considered as one of the main causes of obesity in modern civilizations, and it has been demonstrated that resistance training programs can be used to reduce fat mass. The effects of voluntary exercise on energy metabolism are less clear in adipose tissue. Therefore, the effects of three different voluntary exercise programs on the control of energy metabolism in subcutaneous fat were tested in two different mouse lines. In a cross-over study design, male mice were kept for three or six weeks in the presence or absence of running wheels. For the experiment, mice with increased running capacity (DUhTP) were used and compared to controls (DUC). Body and organ weight, feed intake, and voluntary running wheel activity were recorded. In subcutaneous fat, gene expression of browning markers and mitochondrial energy metabolism were analyzed. Exercise increased heart weight in control mice (p < 0.05) but significantly decreased subcutaneous, epididymal, perinephric, and brown fat mass in both genetic groups (p < 0.05). Gene expression analysis revealed higher expression of browning markers and individual complex subunits present in the electron transport chain in subcutaneous fat of DUhTP mice compared to controls (DUC; p < 0.01), independent of physical activity. While in control mice, voluntary exercise had no effect on markers of mitochondrial fission or fusion, in DUhTP mice, reduced mitochondrial DNA, transcription factor Nrf1, fission- (Dnm1), and fusion-relevant transcripts (Mfn1 and 2) were observed in response to voluntary physical activity (p < 0.05). Our findings indicate that the superior running abilities in DUhTP mice, on one hand, are connected to elevated expression of genetic markers for browning and oxidative phosphorylation in subcutaneous fat. In subcutaneous fat from DUhTP but not in unselected control mice, we further demonstrate reduced expression of genes for mitochondrial fission and fusion in response to voluntary physical activity.
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Metabolismo Energético , Dinâmica Mitocondrial , Condicionamento Físico Animal , Gordura Subcutânea , Animais , Masculino , Camundongos , Tecido Adiposo Marrom/metabolismo , Biomarcadores/metabolismo , Peso Corporal , Metabolismo Energético/genética , Comportamento Alimentar , Regulação da Expressão Gênica , Genes Mitocondriais , Dinâmica Mitocondrial/genética , Tamanho do Órgão , Fosforilação Oxidativa , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Gordura Subcutânea/metabolismo , Fatores de Transcrição/metabolismo , Triglicerídeos/sangueRESUMO
Circadian clocks allow organisms to anticipate repetitive changes in their environment such as food availability, temperature, and predation. While they most clearly manifest at the behavioral level, driving sleep-wake cycles, for example, they also provide critical temporal regulation at the level of individual tissues. Circadian clocks within organs act to ensure that each tissue is functioning in a coordinated manner to anticipate the needs of the organism as a whole but also allow for adaptation of organs to their local environment. One critical aspect of this environment is energy availability, which is communicated at the cellular level via changes in metabolites such as ATP, calcium, and NADH. AMP-activated protein kinase (AMPK) is both sensitive to fluctuations in secondary metabolites and capable of resetting the circadian clock via destabilization of the core clock components CRY and PER. Phosphorylation of serine 71 of CRY1 by AMPK destabilizes CRY1 by decreasing its interaction with binding partner PER2, thus enabling greater association with the SCF complex substrate adaptor FBXL3. Here, we describe a transgenic mouse harboring germline mutation of CRY1 serine 71 to alanine. Unexpectedly, this mutation does not affect the steady-state level of CRY1 protein in mouse livers or quadriceps. We also did not detect changes in either behavioral or molecular circadian rhythms, but female Cry1S71A mice exhibit decreased voluntary locomotor activity compared with wild-type littermates. Together, these findings suggest that phosphorylation of CRY1 serine 71 is not required for the regulation of circadian rhythms under normal physiological conditions. However, it may be involved in responding to metabolic challenges or in other aspects of physiology that contribute to voluntary activity levels.
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Comportamento Animal , Ritmo Circadiano , Criptocromos/metabolismo , Serina/metabolismo , Animais , Criptocromos/química , Feminino , Masculino , Camundongos , FosforilaçãoRESUMO
Mast cells are a type of immune cell widely distributed in the body of vertebrates. Mast cells have many granules that contain several bioactive molecules such as histamine, and these molecules are released through degranulation when the mast cell receives certain stimuli. Because the number of mast cells increases during infection in chickens (Gallus gallus), the activity of mast cells might be related to non-specific symptoms such as anorexia under an infectious condition. Therefore, the purpose of the present study was to investigate whether intraperitoneal (IP) and intracerebroventricular (ICV) injections of compound 48/80, which induces degranulation of mast cells, affects feeding, voluntary activity, cloacal temperature, and the concentrations of plasma corticosterone (CORT) and glucose in chicks. The effect of histamine, which is found in mast cell granules, on these parameters was also investigated. IP injection of compound 48/80 significantly decreased food intake, voluntary activity, and cloacal temperature, and increased plasma CORT concentration in the chicks. While ICV injection of compound 48/80 also decreased food intake, it increased cloacal temperature and plasma glucose concentration. Both IP and ICV injections of histamine significantly decreased food intake, cloacal temperature, and plasma CORT concentration. However, only IP injection of histamine significantly decreased voluntary activity and increased plasma glucose concentration. The results suggest that degranulation of mast cells is related to non-specific symptoms in chicks, although the mechanism seems to be different between peripheral and central tissues. In addition, the effect of peripherally-injected compound 48/80 may be partly mediated by histamine.
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Temperatura Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Histamina/farmacologia , Mastócitos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Glicemia , Galinhas , Corticosterona/sangue , Comportamento Alimentar/efeitos dos fármacos , MasculinoRESUMO
Insulin-like growth factor 2 (IGF2) mRNA binding protein 2 (IMP2) was selectively deleted from adult mouse muscle; two phenotypes were observed: decreased accrual of skeletal muscle mass after weaning and reduced wheel-running activity but normal forced treadmill performance. Reduced wheel running occurs when mice are fed a high-fat diet but is normalized when mice consume standard chow. The two phenotypes are due to altered output from different IMP2 client mRNAs. The reduced fiber size of IMP2-deficient muscle is attributable, in part, to diminished autocrine Igf2 production; basal tyrosine phosphorylation of the insulin and IGF1 receptors is diminished, and Akt1 activation is selectively reduced. Gsk3α is disinhibited, and S536-phosphorylated ε subunit of eukaryotic initiation factor 2B [eIF2Bε(S536)] is hyperphosphorylated. Protein synthesis is reduced despite unaltered mTOR complex 1 activity. The diet-dependent reduction in voluntary exercise is likely due to altered muscle metabolism, as contractile function is normal. IMP2-deficient muscle exhibits reduced fatty acid oxidation, due to a reduced abundance of mRNA of peroxisome proliferator-activated receptor α (PPARα), an IMP2 client, and PPARα protein. IMP2-deficient muscle fibers treated with a mitochondrial uncoupler to increase electron flux, as occurs with exercise, exhibit reduced oxygen consumption from fatty acids, with higher oxygen consumption from glucose. The greater dependence on muscle glucose metabolism during increased oxygen demand may promote central fatigue and thereby diminish voluntary activity.
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Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Comunicação Autócrina , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Insulina/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/metabolismo , PPAR alfa/metabolismo , Fosforilação , Esforço Físico/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD+ dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity. The increased activity was accompanied with increased muscle AMP-activated protein kinase (AMPK) activity. Altogether, these results indicate that overexpression of SIRT6 in mice retards important aspects of the aging process and suggest SIRT6 to be a potential therapeutic target for the treatment of a set of age-related disorders.
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Envelhecimento/metabolismo , Análise Química do Sangue , Longevidade , Sirtuínas/metabolismo , Animais , Composição Corporal , Calorimetria Indireta , DNA/análise , Expressão Gênica , Teste de Tolerância a Glucose , Cabelo/crescimento & desenvolvimento , Immunoblotting , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Análise em Microsséries , Fenótipo , RNA/análise , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Cicatrização/fisiologiaRESUMO
Recent research suggests that long-interval intracortical inhibition (LICI) is followed by a transitory period of late cortical disinhibition (LCD) that can even lead to a net increase in cortical excitability. The relationship between LICI/LCD and voluntary drive remains poorly understood. Our study aims at investigating the influence of index abduction on LICI and LCD in an actively engaged muscle and a neighboring muscle, while varying the intensity of the conditioning stimulus (CS). Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles in 13 subjects. Paired-pulses were delivered with 10 different interstimulus intervals (ranging from 60 to 290 ms). Whatever the condition (relaxed or active FDI), the test stimulus was set to evoke an MEP of 1mV. The time course of conditioned MEP amplitude was compared for relaxed and active conditions when the CS intensity was set to (i) 130% of the rest motor threshold (RMT) or (ii) to evoke the same size of MEP under both conditions. LICI lasted longer (i.e. disinhibition occurred later) at rest than during abduction when evoked either by similar or matched conditioning stimuli. No post-LICI facilitation was observed at rest - even when the CS intensity was set to 160% RMT. In contrast, long-interval intracortical facilitation (LICF) was observed in the quiescent ADM when FDI was active. LICF may then be associated with voluntary activity albeit with lack of topographic specificity.
Assuntos
Córtex Cerebral/fisiologia , Potencial Evocado Motor/fisiologia , Mãos/inervação , Músculo Esquelético/fisiologia , Inibição Neural/fisiologia , Relaxamento/fisiologia , Adulto , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
OBJECTIVE: This research examines whether Beijing residents are more or less likely than Montréal residents to avoid stair climbing, by replicating a study in Montréal, Canada that measured the impacts of distance between stairs and escalator, height between floors and pedestrian volume on stair climbing rate. METHOD: 15 stairways, 14 up-escalators and 13 down-escalators were selected in 13 publicly accessible settings in Beijing. Distance between the bottom or top of nearest stair and escalator combinations varied from 2.1 m to 114.1 m with height between floors varying from 3.3 m to 21.7 m. Simultaneous counts were conducted on stair and escalator pairs, for a total of 37,081 counted individuals. RESULTS: In the ascent model, pedestrian volume accounted for 16.3% of variance in stair climbing, 16.4% when height was added and 45.1% when distance was added. In the descent model, 40.9% of variance was explained by pedestrian volume, 41.5% when height was added and 45.5% when distance was added. CONCLUSION: Separating stairs and escalator is effective in increasing stair climbing in Beijing, accounting for 29% of the variance in stair climbing, compared with 43% in Montreal. As in the Montreal case, distance has less effect on stair use rate when descending. Overall, 25.4% of Beijingers opted for stairs when ascending compared with 20.3% of Montrealers, and for descending 32.8% and 31.1% respectively.