RESUMO
Gut inflammation can trigger neuroinflammation and is linked to mood disorders. Microbiota-derived short-chain fatty acids (SCFAs) can modulate microglia, yet the mechanism remains elusive. Since microglia do not express free-fatty acid receptor (FFAR)2, but intestinal epithelial cells (IEC) and peripheral myeloid cells do, we hypothesized that SCFA-mediated FFAR2 activation within the gut or peripheral myeloid cells may impact microglia inflammation. To test this hypothesis, we developed a tamoxifen-inducible conditional knockout mouse model targeting FFAR2 exclusively on IEC and induced intestinal inflammation with dextran sodium sulfate (DSS), a well-established colitis model. Given FFAR2's high expression in myeloid cells, we also investigated its role by selectively deleting it in these populations of cells. In an initial study, male and female wild-type mice received 0 or 2% DSS for 5d and microglia were isolated 3d later to assess inflammatory status. DSS induced intestinal inflammation and upregulated inflammatory gene expression in microglia, indicating inflammatory signaling via the gut-brain axis. Despite the lack of significant effects of sex in the intestinal phenotype, male mice showed higher microglial inflammatory response than females. Subsequent studies using FFAR2 knockout models revealed that FFAR2 expression in IECs or immune myeloid cells did not affect DSS-induced colonic pathology (i.e. clinical and histological scores and colon length), or colonic expression of inflammatory genes. However, FFAR2 knockout led to an upregulation of several microglial inflammatory genes in control mice and downregulation in DSS-treated mice, suggesting that FFAR2 may constrain neuroinflammatory gene expression under healthy homeostatic conditions but may permit it during intestinal inflammation. No interactions with sex were observed, suggesting sex does not play a role on FFAR2 potential function in gut-brain communication in the context of colitis. To evaluate the role of FFAR2 activated by microbiota-derived SCFAs, we employed the same knockout and DSS models adding fermentable dietary fiber (0 or 2.5% inulin for 8 wks). Despite no genotype or fiber main effects, contrary to our hypothesis, inulin feeding augmented DSS-induced inflammation and signs of colitis, suggesting context-dependent effects of fiber. These findings highlight microglial involvement in colitis-associated neuroinflammation and advance our understanding of FFAR2's role in the gut-brain axis. Although not integral, we observed that the role of FFAR2 differs between homeostatic and inflammatory conditions, underscoring the need to consider different inflammatory conditions and disease contexts when investigating the role of FFAR2 and SCFAs in the gut-brain axis.
Assuntos
Colite , Microglia , Animais , Feminino , Masculino , Camundongos , Colo/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Células Epiteliais/patologia , Inflamação/metabolismo , Inulina/efeitos adversos , Inulina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides , Doenças Neuroinflamatórias , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Background: Several studies have reported that marathon runners have a higher risk of upper respiratory tract infections (URTI) post marathon than non-exercising controls. However, other studies did not find a higher risk of URTI in the same participants before and after a marathon, precluding a conclusive consensus. Besides the between-subjects effects, another important confounding factor in these results is the different pre and post follow-up time to track URTI. Objectives: Identify by meta-analysis whether a marathon Running increases the risk of URTI, adjusting the follow-up time to track URTI. Data sources: We searched for articles using MEDLINE (PubMed), Embase, Scopus, Web of Science, the Cochrane Library, and EBSCOhost, combining the marathon and respiratory infection descriptor synonyms, on 1st December 2022. Eligibility criteria: The PICOS framework included human population, comparison between pre and post marathon running, of URTI symptoms (assessed from one to 4 weeks), in noncontrolled intervention studies. Data Synthesis: Because follow-up was longer before the marathon in many studies, we adjusted the number of subjects with infections before marathon to the equivalent post-marathon follow-up duration. There was 18% higher incidence of URTI post-marathon (OR 1.18 95%CI [1.05-1.33], p= 0.005) in a very consistent meta-analysis (I2 = 0%, p = 0.69), with no risk of publication bias (Egger test p-value = 0.82) for the 7 studies included. The main issues with quality of the studies were bias in measuring the outcome, bias in classification of intervention (participation in the marathon) and time-varying confounding (corrected for analysis), and therefore the quality of evidence was moderate (GRADE approach = 3). Limitations: The need for follow-up time adjustment is a limitation, since the number of URTI recorded could be different if the original studies had used the same follow-up time pre and post marathon. The subjectivity of the URTI assessments is another limitation in this field. Conclusions: There is an increased risk of URTI post marathon running and research on this topic to understand mechanisms might support runners to find efficient interventions to reduce this risk. Protocol: Protocol registration on in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022380991.
Assuntos
Corrida de Maratona , Infecções Respiratórias , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Fatores de Risco , Exercício Físico/fisiologia , Corrida/fisiologia , Sistema Imunitário , RiscoRESUMO
The gastrointestinal tract contains trillions of microbes (collectively known as the gut microbiota) that play essential roles in host physiology and health. Studies from our group and others have demonstrated that exercise independently alters the composition and functional capacity of the gut microbiota. Here, we review what is known about the gut microbiota, how it is studied, and how it is influenced by exercise training and discuss the potential mechanisms and implications for human health and disease.
Assuntos
Exercício Físico , Microbioma Gastrointestinal , Trato Gastrointestinal/fisiologia , Animais , HumanosRESUMO
KEY POINTS: Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults. These findings provide novel cellular mechanisms for the beneficial effects of exercise in obese adults. ABSTRACT: Circulating progenitor cells (CPCs) and subpopulations are normally found in the bone marrow, but can migrate to peripheral tissues to participate in local inflammation and/or remodelling. The purpose of this study was to compare the CPC response, particularly the inflammatory-primed haematopoietic stem and progenitor (HSPC) subpopulation, to a 6 week endurance exercise training (EET) intervention between lean and obese adults. Seventeen healthy weight (age: 23.9 ± 5.4 years, body mass index (BMI): 22.0 ± 2.6 kg m-2 ) and 10 obese (age: 29.0 ± 8.0 years, BMI: 33.1 ± 6.0 kg m-2 ) previously sedentary adults participated in an EET. Blood was collected before and after EET for quantification of CPCs and subpopulations via flow cytometry, colony forming unit assays and plasma concentrations of C-X-C motif chemokine 12 (CXCL12), granulocyte-colony stimulating factor (G-CSF), and chemokine (C-C motif) ligand 2 (CCL2). Exercise training reduced the number of circulating HSPCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs). EET increased the colony forming potential of granulocytes and macrophages irrespective of BMI. EET reduced the number of HSPCs expressing the chemokine receptor CCR2 and the pro-inflammatory marker TLR4. EET-induced changes in adipose tissue-derived MSCs and bone marrow-derived MSCs were negatively related to changes in absolute fitness. Our results indicate that EET, regardless of BMI status, decreases CPCs and subpopulations, particularly those primed for contribution to tissue inflammation.
Assuntos
Terapia por Exercício/métodos , Inflamação/sangue , Inflamação/terapia , Obesidade/complicações , Células-Tronco/citologia , Magreza/complicações , Adulto , Células Cultivadas , Feminino , Humanos , Inflamação/etiologia , Masculino , Resistência Física , Células-Tronco/metabolismo , Adulto JovemRESUMO
Many factors are involved in weight gain and metabolic disturbances associated with obesity. The gut microbiota has been of particular interest in recent years, since both human and animal studies have increased our understanding of the delicate symbiosis between the trillions of microbes that reside in the GI tract and the host. It has been suggested that disruption of this mutual tolerance may play a significant role in modulating host physiology during obesity. Environmental influences such as diet, exercise, and early life exposures can significantly impact the composition of the microbiota, and this dysbiosis can in turn lead to increased host adiposity via a number of different mechanisms. The ability of the microbiota to regulate host fat deposition, metabolism, and immune function makes it an attractive target for achieving sustained weight loss.
Assuntos
Microbioma Gastrointestinal , Obesidade/microbiologia , Obesidade/fisiopatologia , Animais , Dieta , Metabolismo Energético , Homeostase , Humanos , InflamaçãoRESUMO
There is robust evidence that habitual physical activity is anti-inflammatory and protective against developing chronic inflammatory disease. Much less is known about the effects of habitual moderate exercise in the gut, the compartment that has the greatest immunological responsibility and interactions with the intestinal microbiota. The link between the two has become evident, as recent studies have linked intestinal dysbiosis, or the disproportionate balance of beneficial to pathogenic microbes, with increased inflammatory disease susceptibility. Limited animal and human research findings imply that exercise may have a beneficial role in preventing and ameliorating such diseases by having an effect on gut immune function and, recently, microbiome characteristics. Emerging data from our laboratory show that different forms of exercise training differentially impact the severity of intestinal inflammation during an inflammatory insult (for example, ulcerative colitis) and may be jointly related to gut immune cell homeostasis and microbiota-immune interactions. The evidence we review and present will provide data in support of rigorous investigations concerning the effects of habitual exercise on gut health and disease.
Assuntos
Colite/imunologia , Colo/imunologia , Exercício Físico/fisiologia , Intestinos/imunologia , Microbiota/imunologia , Animais , Colite/terapia , Colo/microbiologia , Terapia por Exercício , Homeostase , Humanos , Imunidade nas Mucosas/imunologia , Intestinos/microbiologiaRESUMO
Previous research has examined the effects of exercise in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. However, all previous studies have utilized a chronic model of EAE, with exercise delivered prior to or immediately after induction of EAE. To our knowledge, no study has examined the effects of exercise delivered during a remission period after initial disease onset in a relapsing-remitting model of EAE (RR-EAE). The current study examines the effects of both voluntary wheel running and forced treadmill exercise on clinical disability and hippocampal brain-derived neurotrophic factor (BDNF) in SJL mice with RR-EAE. The results demonstrate no significant effects of exercise delivered during remission after initial disease onset on clinical disability scores or levels of hippocampal BDNF in mice with RR-EAE. Furthermore, our results demonstrate no significant increase in citrate synthase activity in the gastrocnemius and soleus muscles of mice in the running wheel or treadmill conditions compared with the sedentary condition. These results suggest that the exercise stimuli might have been insufficient to elicit differences in clinical disability or hippocampal BDNF among treatment conditions. © 2016 Wiley Periodicals, Inc.
Assuntos
Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citrato (si)-Sintase/metabolismo , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/patologia , Teste de Esforço , Feminino , Adjuvante de Freund/toxicidade , Hipocampo/metabolismo , Camundongos , Atividade Motora/fisiologia , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Músculos/patologia , Proteína Proteolipídica de Mielina/imunologia , Proteína Proteolipídica de Mielina/toxicidade , Tamanho do Órgão , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/toxicidade , Distribuição Aleatória , Recidiva , Corrida/fisiologia , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
NEW FINDINGS: What is the central question of this study? Do older and younger adults have similar vascular endothelial and blood pressure responses to acute inflammation? Does physical activity affect these responses? What is the main finding and its importance? Older adults reduce blood pressure whereas younger adults reduce endothelial function during acute inflammation. Physical activity does not provide protection against these inflammation-induced changes. This is important because older adults regularly experience acute increases in systemic inflammation that may predispose older adults to cardiovascular events through dysregulation of blood pressure. Ageing is characterized by chronic, low-grade inflammation that is related to endothelial dysfunction and arterial stiffness. Physical activity can protect older adults (OAs) from cardiovascular dysfunction and increased inflammation. Acute inflammation causes transient endothelial dysfunction and arterial stiffening in younger adults (YAs), but may not have the same effect in OAs. We hypothesized that acute inflammation would increase blood pressure (BP) and endothelial impairment to a greater extent in OAs versus YAs, but that physical activity would be protective. We induced inflammation with an influenza vaccine in 22 OAs (55-75 years old) and 31 YAs (18-35 years old) and measured brachial flow-mediated dilatation (FMD), BP and serum inflammatory markers before vaccination and at 24 and 48 h afterwards. Physical activity data were collected using accelerometry. During inflammation, only OAs reduced systolic BP (from 120 ± 3 to 115 ± 2 to 115 ± 3 mmHg, P < 0.05), but only YAs reduced FMD (from 11.3 ± 0.7 to 8.5 ± 0.6 to 8.9 ± 0.6% in YAs and from 6.7 ± 0.6 to 5.3 ± 0.7 to 6.0 ± 0.6% in OAs, P < 0.05 for time and interaction effects). The entire cohort increased C-reactive protein (P < 0.05), but only YAs increased interleukin-6 (P < 0.05 for time × age group interaction). Physical activity was related to the percentage change in inflammation in OAs (r = -0.50, P < 0.05) but not to the change in arterial function in either group (P > 0.05 for all). We conclude that acute inflammation reduced FMD only in YAs and reduced BP only in OAs. Physical activity did not affect arterial function during acute inflammation. Clinicians should be aware that all OAs are vulnerable to inflammation-mediated reductions in BP and cardiovascular complications.
Assuntos
Envelhecimento/fisiologia , Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiopatologia , Exercício Físico/fisiologia , Inflamação/fisiopatologia , Adulto , Fatores Etários , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/induzido quimicamente , Mediadores da Inflamação/metabolismo , Vacinas contra Influenza/efeitos adversos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologia , Rigidez Vascular/fisiologiaRESUMO
BACKGROUND: Dietary fiber intake leading to short-chain fatty acid (SCFA) production could be a strategy to combat intermittent bouts of inflammation during ulcerative colitis. OBJECTIVE: Our objective was to evaluate dietary potato fiber (PF) in attenuating inflammation using a dextran sodium sulfate (DSS)-induced colitis mouse model. We hypothesized that PF would show anti-inflammatory effects compared with cellulose due in part to SCFA production. METHODS: Male C57Bl/6J mice were fed diets containing either 8% cellulose or 14.5% PF for a 22-d feeding study. Starting on study day 14, mice were provided either distilled water (control) or 2% (wt:vol) DSS in drinking water for 5 d (cellulose+control, n = 17; PF+control, n = 16; cellulose+DSS, n = 17; and PF+DSS, n = 16). Body weights and food and water intakes were collected daily from day 14 through day 22. Distal colon tissue was analyzed for histologic outcomes and changes in gene expression, and cecal contents were analyzed for SCFA concentrations. Data were analyzed by ANOVA, with repeated measures applied where necessary. RESULTS: At day 5 post-DSS induction, cellulose+DSS mice exhibited a 2% reduction (P < 0.05) in body weight compared with PF+DSS and PF+ and cellulose+control mice. PF+DSS mice had greater (P < 0.05) cecal butyrate concentrations [24.5 µmol/g dry matter (DM)] than did cellulose+DSS mice (4.93 µmol/g DM). Mice fed PF+DSS had lower (P < 0.05) infiltration of leukocytes in the distal colon than did mice fed cellulose+DSS (mean histology scores of 1.22 and 2.30, respectively). Furthermore, mice fed cellulose+DSS exhibited 1.42, 11.5, 8.48, and 35.5 times greater (P < 0.05) colon mRNA expression of tumor necrosis factor α (Tnfa) and interleukin (Il) 1b, Il6, and Il17a, respectively, and 7.10 times greater (P < 0.05) expression of C-X-C motif ligand 1 (Cxc1) compared with mice fed PF+DSS. CONCLUSIONS: These results suggest that PF fed to mice before and during DSS colitis attenuates inflammation, potentially through SCFA production; however, future studies are needed to understand the role of dietary fiber intake and immune activation.
Assuntos
Colite/prevenção & controle , Colite/fisiopatologia , Fibras na Dieta/administração & dosagem , Fermentação , Inflamação/prevenção & controle , Solanum tuberosum , Animais , Anti-Inflamatórios , Celulose/administração & dosagem , Colite/induzido quimicamente , Colo/química , Sulfato de Dextrana/administração & dosagem , Dieta , Modelos Animais de Doenças , Ácidos Graxos Voláteis/biossíntese , Interleucina-17/genética , Interleucina-1beta/genética , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Fator de Necrose Tumoral alfa/genéticaRESUMO
African-American (AA) men have higher arterial stiffness and augmentation index (AIx) than Caucasian-American (CA) men. Women have greater age-associated increases in arterial stiffness and AIx than men. This study examined racial and sex differences in arterial stiffness and central hemodynamics at rest and after an acute bout of maximal exercise in young healthy individuals. One hundred young, healthy individuals (28 AA men, 24 AA women, 25 CA men, and 23 CA women) underwent measurements of aortic blood pressure (BP) and arterial stiffness at rest and 15 and 30 min after an acute bout of graded maximal aerobic exercise. Aortic BP and AIx were derived from radial artery applanation tonometry. Aortic stiffness (carotid-femoral) was measured via pulse wave velocity. Aortic stiffness was increased in AA subjects but not in CA subjects (P < 0.05) after an acute bout of maximal cycling exercise, after controlling for body mass index. Aortic BP decreased after exercise in CA subjects but not in AA subjects (P < 0.05). Women exhibited greater reductions in AIx after maximal aerobic exercise compared with men (P < 0.05). In conclusion, race and sex impact vascular and central hemodynamic responses to exercise. Young AA and CA subjects exhibited differential responses in central stiffness and central BP after acute maximal exercise. Premenopausal women had greater augmented pressure at rest and after maximal aerobic exercise than men. Future research is needed to examine the potential mechanisms.
Assuntos
População Negra , Pressão Sanguínea , Exercício Físico , Rigidez Vascular , População Branca , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pré-Menopausa/fisiologia , Fatores SexuaisRESUMO
Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and ß-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.
Assuntos
Endotélio Vascular/fisiopatologia , Exercício Físico , Inflamação/prevenção & controle , Vacinas contra Influenza/efeitos adversos , Rigidez Vascular , Vasodilatação , Fatores Etários , Idoso , Estudos Cross-Over , Feminino , Frequência Cardíaca , Humanos , Illinois , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Fatores de TempoRESUMO
OBJECTIVE(S): Peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes prolonged depressive-like behavior in aged mice that is dependent on indoleamine 2,3 dioxygenase (IDO) activation. Regular moderate-intensity exercise training has been shown to exert neuroprotective effects that might reduce depressive-like behavior in aged mice. The purpose of this study was to test the hypothesis that voluntary wheel running (VWR) would attenuate LPS-induced depressive-like behavior and brain IDO gene expression in 4- and 22-month-old C57BL/6J mice. METHODS: Mice were housed with a running wheel (VWR) or no wheel (standard) for 30 (young adult mice) or 70 days (aged mice), after which they were intraperitoneally injected with LPS (young adult mice: 0.83 mg/kg; aged mice: 0.33 mg/kg). RESULTS: Young adult VWR mice ran on average 6.9 km/day, while aged VWR mice ran on average 3.4 km/day. Both young adult and aged VWR mice increased their forced exercise tolerance compared to their respective standard control groups. VWR had no effect on LPS-induced anorexia, weight loss, increased immobility in the tail suspension test and decreased sucrose preference in either young adult or aged mice. Four (young adult mice) and 24 h (aged mice) after injection of LPS, mRNA transcripts for TNF-α, IL-1ß, IL-6, and IDO were upregulated in the whole brain independently of VWR. CONCLUSION: Prolonged physical exercise has no effect on the neuroinflammatory response to LPS and its behavioral consequences in young adult and aged mice.
Assuntos
Envelhecimento/fisiologia , Depressão/induzido quimicamente , Depressão/reabilitação , Terapia por Exercício/métodos , Lipopolissacarídeos/toxicidade , Corrida , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Teste de Esforço , Fadiga/induzido quimicamente , Preferências Alimentares/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Elevação dos Membros Posteriores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perfil de Impacto da DoençaRESUMO
The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.
Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Hipocampo/anatomia & histologia , Memória/fisiologia , Percepção Espacial/fisiologia , Idoso , Fator Neurotrófico Derivado do Encéfalo/sangue , Ensaio de Imunoadsorção Enzimática , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
The primary purpose of this feasibility study was to establish a correlation between pro-inflammatory cytokine accumulation and severity of tissue damage during local pressure with various temperatures. The secondary purpose was to compare skin blood flow patterns for assessing the efficacy of local cooling on reducing skin ischemia under surface pressure. Eight Sprague-Dawley rats were assigned to two protocols, including pressure with local cooling (Δt = -10 °C) and pressure with local heating (Δt = 10 °C). Pressure of 700 mmHg was applied to the right trochanter area of rats for 3 h. Skin perfusion quantified by laser Doppler flowmetry and TNF-∗ and IL-1ß levels were measured. Our results showed that TNF-α concentrations were increased more significantly with local heating than with local cooling under pressure whereas IL-1ß did not change. Our results support the notion that weight bearing soft tissue damage may be reduced through temperature modulation and that non-invasive perfusion measurements using laser Doppler flowmetry may be capable of assessing viability. Furthermore, these results show that perfusion response to loading pressure may be correlated with changes in local pro-inflammatory cytokines. These relationships may be relevant for the development of cooling technologies for reducing risk of pressure ulcers.
Assuntos
Temperatura Baixa , Citocinas/análise , Pele/irrigação sanguínea , Pele/química , Animais , Estudos de Viabilidade , Masculino , Pressão , Ratos Sprague-Dawley , Propriedades de SuperfícieRESUMO
Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.
Assuntos
Envelhecimento , Microbioma Gastrointestinal , Inflamação , Animais , Envelhecimento/imunologia , Microbioma Gastrointestinal/imunologia , Camundongos , Inflamação/imunologia , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , MasculinoRESUMO
Peripheral stimulation of the innate immune system with LPS causes exaggerated neuroinflammation and prolonged sickness behavior in aged mice. Regular moderate intensity exercise has been shown to exert anti-inflammatory effects that may protect against inappropriate neuroinflammation and sickness in aged mice. The purpose of this study was to test the hypothesis that voluntary wheel running would attenuate LPS-induced sickness behavior and proinflammatory cytokine gene expression in ~22-month-old C57BL/6J mice. Mice were housed with a running wheel (VWR), locked-wheel (Locked), or no wheel (Standard) for 10 weeks, after which they were intraperitoneally injected with LPS across a range of doses (0.02, 0.08, 0.16, 0.33 mg/kg). VWR mice ran on average 3.5 km/day and lost significantly more body weight and body fat, and increased their forced exercise tolerance compared to Locked and Shoebox mice. VWR had no effect on LPS-induced anorexia, adipsia, weight-loss, or reductions in locomotor activity at any LPS dose when compared to Locked and Shoebox groups. LPS induced sickness behavior in a dose-dependent fashion (0.33>0.02 mg/kg). Twenty-four hours post-injection (0.33 mg/kg LPS or Saline) we found a LPS-induced upregulation of whole brain TNFα, IL-1ß, and IL-10 mRNA, and increased IL-1ß and IL-6 in the spleen and liver; these effects were not attenuated by VWR. We conclude that VWR does not reduce LPS-induced exaggerated or prolonged sickness behavior in aged animals, or 24h post-injection (0.33 mg/kg LPS or Saline) brain and peripheral proinflammatory cytokine gene expression. The necessity of the sickness response is critical for survival and may outweigh the subtle benefits of exercise training in aged animals.
Assuntos
Envelhecimento/psicologia , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos , Corrida/psicologia , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/genética , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Fadiga/psicologia , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , RNA/biossíntese , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The purpose of this study was to examine whether exercise training reduced inflammation and symptomology in a mouse model of colitis. We hypothesized that moderate forced treadmill running (FTR) or voluntary wheel running (VWR) would reduce colitis symptoms and colon inflammation in response to dextran sodium sulfate (DSS). Male C57Bl/6J mice were randomized to sedentary, moderate intensity FTR (8-12 m/min, 40 min, 6 weeks, 5x/week), or VWR (30 days access to wheels). DSS was given at 2% (w/v) in drinking water over 5 days. Mice discontinued exercise 24 h prior to and during DSS treatment. Colons were harvested on Days 6, 8 and 12 in FTR and Day 8 post-DSS in VWR experiments. Contrary to our hypothesis, we found that moderate FTR exacerbated colitis symptomology and inflammation as measured by significant (p<0.05) increases in diarrhea and IL-6, IL-1ß, IL-17 colon gene expression. We also observed higher mortality (3/10 died vs. 0/10, p=0.07) in the FTR/DSS group. In contrast, VWR alleviated colitis symptoms and reduced inflammatory gene expression in the colons of DSS-treated mice (p<0.05). While DSS treatment reduced food/fluid intake and body weight, there was a tendency for FTR to exacerbate, and for VWR to attenuate, this effect. FTR (in the absence of DSS) increased gene expression of the chemokine and antibacterial protein CCL6 suggesting that FTR altered gut homeostasis that may be related to the exaggerated response to DSS. In conclusion, we found that FTR exacerbated, whereas VWR attenuated, symptoms and inflammation in response to DSS.
Assuntos
Colite/prevenção & controle , Inflamação/etiologia , Inflamação/prevenção & controle , Condicionamento Físico Animal/efeitos adversos , Corrida , Estresse Psicológico/patologia , Animais , Quimiocinas CC/biossíntese , Colite/etiologia , Colite/imunologia , Dextranos/administração & dosagem , Modelos Animais de Doenças , Inflamação/mortalidade , Masculino , Camundongos , Distribuição Aleatória , Corrida/psicologia , Estresse Psicológico/etiologia , Estresse Psicológico/mortalidade , Sulfatos/administração & dosagem , Redução de PesoRESUMO
The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Exercício Físico/fisiologia , Fator de Crescimento Insulin-Like I/análise , Plasticidade Neuronal/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Encéfalo/fisiologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Fator de Crescimento Insulin-Like I/fisiologia , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Aptidão Física/fisiologia , Lobo Temporal/fisiologia , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
OBJECTIVES: To investigate the efficacy of local cooling on reducing sacral skin ischemia in a weight-bearing position, and to identify the underlying physiological mechanisms using wavelet-based spectrum analysis of reactive hyperemia in people with spinal cord injury (SCI). DESIGN: Repeated-measures and before-after trial design. SETTING: University research laboratory. PARTICIPANTS: Wheelchair users with SCI with injury level between C4 and T5 (n=10) and able-bodied controls (n=10). INTERVENTIONS: Three protocols consisting of pressure without temperature changes, pressure with local cooling (Δt=-10°C), and pressure with local heating (Δt=+10°C) were tested. Each protocol consisted of a 10-minute baseline period, a 20-minute loading period at 60 mmHg, and a 20-minute recovery period (reactive hyperemia). A 30-minute washout period was allowed between protocols. MAIN OUTCOME MEASURES: A compound sensor head consisting of laser Doppler and heating and cooling probes was used to measure sacral skin blood flow and control skin temperature. Reactive hyperemic response to pressure and temperature stimuli was characterized in the time and frequency (metabolic [.0095-.02 Hz], neurogenic [.02-.05 Hz], and myogenic [.05-.15 Hz] components) domains. RESULTS: Pressure with local cooling resulted in a smaller reactive hyperemic response in both people with SCI and able-bodied controls as compared with pressure with local heating (P<.017) and pressure without temperature changes (P<.017), and the smaller hyperemia was attributed to reduced metabolic and neurogenic activities. People with SCI showed an attenuated response in reactive hyperemia (P<.017). CONCLUSIONS: This study supports the concept of using local cooling to reduce skin ischemia under surface pressure in people with SCI.
Assuntos
Hiperemia/prevenção & controle , Isquemia/prevenção & controle , Sacro , Temperatura Cutânea , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Masculino , Úlcera por Pressão/prevenção & controle , Pele/irrigação sanguínea , Suporte de Carga , Cadeiras de RodasRESUMO
OBJECTIVE: To compare the efficacy of wheelchair tilt-in-space and recline on enhancing muscle and skin perfusion over the ischial tuberosities in people with spinal cord injury (SCI). DESIGN: Repeated-measures and before-after trial design. SETTING: University research laboratory. PARTICIPANTS: Power wheelchair users with SCI (N=20). INTERVENTIONS: Six combinations of wheelchair tilt-in-space and recline angles were presented to participants in a random order. The testing protocol consisted of a baseline 5 minutes sitting with no tilt/recline and 5 minutes positioned in a tilted and reclined position at each of 6 conditions, including: (1) 15° tilt-in-space and 100° recline, (2) 25° tilt-in-space and 100° recline, (3) 35° tilt-in-space and 100° recline, (4) 15° tilt-in-space and 120° recline, (5) 25° tilt-in-space and 120° recline, and (6) 35° tilt-in-space and 120° recline. MAIN OUTCOME MEASURES: Muscle and skin perfusion were assessed by near-infrared spectroscopy and laser Doppler flowmetry, respectively. RESULTS: Muscle perfusion was significantly increased at 25° and 35° tilt-in-space when combined with 120° recline, and skin perfusion was significantly increased at 3 tilt-in-space angles (15°, 25°, 35°) when combined with 120° recline and at 35° tilt-in-space when combined with 100° recline (P<.05). Even in the positions of increased muscle perfusion and skin perfusion (25° and 35° of tilt-in-space combined with 120° of recline), the amount of muscle perfusion change was significantly lower than the amount of skin perfusion change (P<.05). CONCLUSIONS: Our results indicate that a larger angle of tilt-in-space and recline is needed to improve muscle perfusion compared with skin perfusion. A position of 25° tilt-in-space combined with 120° recline is effective in enhancing muscle and skin perfusion of weight-bearing soft tissues at the ischial tuberosities.