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Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T-regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti-inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.
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Background: /Aims: Epidemiological data show that there is an important relationship between respiratory and intestinal diseases. To improve our understanding on the interconnectedness between the lung and intestinal mucosa and the overlap between respiratory and intestinal diseases, our aim was to investigate the influence of ovalbumin (OVA)-induced allergic airway inflammation on gut homeostasis. Methods: A/J mice were sensitized and challenged with OVA. The animals were euthanized 24 h after the last challenge, lung inflammation was determined by evaluating cells in Bronchoalveolar lavage fluid, serum anti-OVA IgG titers and colon morphology, inflammation and integrity of the intestinal mucosa were investigated. IL-4 and IL-13 levels and myeloperoxidase activity were determined in the colon samples. The expression of genes involved in inflammation and mucin production at the gut mucosa was also evaluated. Results: OVA challenge resulted not only in lung inflammation but also in macroscopic alterations in the gut such as colon shortening, increased myeloperoxidase activity and loss of integrity in the colonic mucosal. Neutral mucin intensity was lower in the OVA group, which was followed by down-regulation of transcription of ATOH1 and up-regulation of TJP1 and MUC2. In addition, the OVA group had higher levels of IL-13 and IL-4 in the colon. Ova-specific IgG1 and OVA-specific IgG2a titers were higher in the serum of the OVA group than in controls. Conclusions: Our data using the OVA experimental model suggested that challenges in the respiratory system may result not only in allergic airway inflammation but also in the loss of gut homeostasis.
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The assessment of the enteric nervous system provides a better understanding of the effects that contaminants can have on the health and well-being of organisms. It has been reported that 2,4-dichlorophenoxyacetic acid (2,4-D) is a highly persistent herbicide in the environment that is responsible for neurotoxic changes in different myenteric neuronal subpopulations. The current study aimed to evaluate the effects of 2,4-D on myenteric neurons in the colon of Rattus norvegicus for the first time. A dose of 2,4-D (5 mg/kg/day) was administered to the experimental group (2,4-D) for 15 days. Then, the proximal colon was collected and submitted to Giemsa and NADPH-d histochemical techniques for the disclosure of total and nitrergic neurons. The 2,4-D group presented a higher density of total neurons (p = 0.05, t-test), which together with the maintenance of nitrergic neuronal density, may be related to the increase in the expression of the neurotransmitter acetylcholine by colocalization, responsible for stimulating the intestinal smooth muscle and increasing the chances of the expulsion of the harmful content present in the lumen. Over 15 days, the neurotoxic effects of 2,4-D in the myenteric plexus influenced an increase in the general population of myenteric neurons in the colon.
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Herbicidas , Neurônios Nitrérgicos , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Colo/metabolismo , Herbicidas/metabolismo , Herbicidas/toxicidade , Humanos , Plexo Mientérico/metabolismo , Neurônios Nitrérgicos/metabolismo , RatosRESUMO
Brown adipose tissue (BAT) is a potential target to treat obesity and diabetes, dissipating energy as heat. Type 2 diabetes (T2D) has been associated with obesogenic diets; however, T2D was also reported in lean individuals to be associated with genetic factors. We aimed to investigate the differences between obese and lean models of insulin resistance (IR) and elucidate the mechanism associated with BAT metabolism and dysfunction in different IR animal models: a genetic model (lean GK rats) and obese models (diet-induced obese Wistar rats) at 8 weeks of age fed a high-carbohydrate (HC), high-fat (HF) diet, or high-fat and high-sugar (HFHS) diet for 8 weeks. At 15 weeks of age, BAT glucose uptake was evaluated by 18F-FDG PET under basal (saline administration) or stimulated condition (CL316,243, a selective ß3-AR agonist). After CL316, 243 administrations, GK animals showed decreased glucose uptake compared to HC animals. At 16 weeks of age, the animals were euthanized, and the interscapular BAT was dissected for analysis. Histological analyses showed lower cell density in GK rats and higher adipocyte area compared to all groups, followed by HFHS and HF compared to HC. HFHS showed a decreased batokine FGF21 protein level compared to all groups. However, GK animals showed increased expression of genes involved in fatty acid oxidation (CPT1 and CPT2), BAT metabolism (Sirt1 and Pgc1-α), and obesogenic genes (leptin and PAI-1) but decreased gene expression of glucose transporter 1 (GLUT-1) compared to other groups. Our data suggest impaired BAT function in obese Wistar and GK rats, with evidence of a whitening process in these animals.
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Tecido Adiposo Marrom/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica , Fluordesoxiglucose F18 , Glucose/metabolismo , Masculino , Tomografia por Emissão de Pósitrons , Ratos , Ratos WistarRESUMO
BACKGROUND: Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model. METHODS: Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals. KEY RESULTS: We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1ß concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1ß reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls. CONCLUSIONS: The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
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Diabetes Mellitus Tipo 2/fisiopatologia , Trânsito Gastrointestinal , Resistência à Insulina , Intestino Delgado/fisiopatologia , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Duodeno/inervação , Duodeno/metabolismo , Duodeno/fisiopatologia , Íleo/inervação , Íleo/metabolismo , Íleo/fisiopatologia , Mediadores da Inflamação/metabolismo , Intestino Delgado/inervação , Intestino Delgado/metabolismo , Jejuno/inervação , Jejuno/metabolismo , Jejuno/fisiopatologia , Masculino , Plexo Mientérico/fisiopatologia , Ratos Wistar , Plexo Submucoso/fisiopatologiaRESUMO
Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1ß and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.
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Obesidade/sangue , Obesidade/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Butiratos/sangue , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Técnicas de Inativação de Genes , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Receptores Acoplados a Proteínas G/genética , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
The role of neutrophils in cancer is still very contradictory. Several studies have demonstrated the cytotoxic capacity of neutrophils against different types of tumors, by releasing inflammatory cytokines, ROS and activating other immune cells. On the other hand, recent papers have claimed the protumorigenic action of neutrophils, mainly by changing their phenotype and producing cytokines that promote tumor growth. In this context, this study aimed to evaluate neutrophil action and function during tumor development. To do so, we used male Wistar rats inoculated with Walker 256 breast carcinoma. Tumor, circulating neutrophils and bone marrow were studied in the following time points after tumor inoculation: 12 h, 24 h, 48 h, 3 d, 5 d, 7 d, 10 d, and 14 d, in order to analyze neutrophil migration kinetics, circulating neutrophil phenotype and bone marrow response to the tumor growth. Herein, our results demonstrated that W256T was unable to trigger an intratumoral inflammatory response after 5 days of tumor development and consequently, from that point on, prevented neutrophil migration to its microenvironment. Also, the tumor changed circulating neutrophil phenotype by up-regulating inflammation-related genes. Even though circulating neutrophils were entirely able to respond to an inflammatory stimulus, they did not recognize and attack the tumor, allowing the tumor to grow without any immune interference. To promote the entry of neutrophils into the tumor microenvironment, LPS was injected intratumorally. Neutrophil migration and activation due to LPS injection resulted in complete tumor regression in all subjects. In conclusion, activating neutrophils, within the tumor, turned the carcinoma into a recognizable immune target and eliminated it.
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Neoplasias/imunologia , Neoplasias/patologia , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Animais , Biópsia , Movimento Celular , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Lipopolissacarídeos/imunologia , Masculino , Neoplasias/genética , Neoplasias/metabolismo , Ativação de Neutrófilo/genética , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Ratos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Aging can promote significant morphofunctional changes in the gastrointestinal tract (GIT). Regulation of GIT motility is mainly controlled by the myenteric neurons of the enteric nervous system. Actions that aim at decreasing the aging effects in the GIT include those related to diet, with caloric restriction (CR). The CR is achieved by controlling the amount of food or by manipulating the components of the diet. Therefore, the objective of this study was to evaluate different levels of CR on the plasticity of nicotinamide adenine dinucleotide phosphate- (NADPH-) reactive myenteric neurons in the colon of Wistar rats during the aging process using ultrastructural (transmission electron microscopy) and morphoquantitative analysis. Wistar male rats (Rattus norvegicus) were distributed into 4 groups (n = 10/group): C, 6-month-old animals; SR, 18-month-old animals fed a normal diet; CRI, 18-month-old animals fed a 12% CR diet; CRII, 18-month-old animals fed a 31% CR diet. At 6 months of age, animals were transferred to the laboratory animal facility, where they remained until 18 months of age. Animals of the CRI and CRII groups were submitted to CR for 6 months. In the ultrastructural analysis, a disorganization of the periganglionar matrix with the aging was observed, and this characteristic was not observed in the animals that received hypocaloric diet. It was observed that the restriction of 12.5% and 31% of calories in the diet minimized the increase in density and cell profile of the reactive NADPH neurons, increased with age. This type of diet may be adapted against gastrointestinal disturbances that commonly affect aging individuals.
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Envelhecimento , Restrição Calórica , Colo/inervação , Gânglios Autônomos/crescimento & desenvolvimento , Plexo Mientérico/crescimento & desenvolvimento , Plasticidade Neuronal , Neurônios Nitrérgicos/fisiologia , Animais , Biomarcadores/metabolismo , Contagem de Células , Colo/crescimento & desenvolvimento , Colo/fisiologia , Colo/ultraestrutura , Colo Ascendente/crescimento & desenvolvimento , Colo Ascendente/inervação , Colo Ascendente/fisiologia , Colo Ascendente/ultraestrutura , Colo Descendente/crescimento & desenvolvimento , Colo Descendente/inervação , Colo Descendente/fisiologia , Colo Descendente/ultraestrutura , Gânglios Autônomos/citologia , Gânglios Autônomos/fisiologia , Gânglios Autônomos/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Plexo Mientérico/citologia , Plexo Mientérico/fisiologia , Plexo Mientérico/ultraestrutura , NADPH Desidrogenase/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuroproteção , Neurônios Nitrérgicos/citologia , Neurônios Nitrérgicos/ultraestrutura , Tamanho do Órgão , Especificidade de Órgãos , Ratos WistarRESUMO
Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats) and the environmental (HFD-induced obese rats) influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight) was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT) expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn't present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3ß. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given time point of this study, we may conclude that only GK rats shown to be a reliable model to study T2DM.
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Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Obesidade/fisiopatologia , Animais , RatosRESUMO
Obesogenic diets increase body weight and cause insulin resistance (IR), however, the association of these changes with the main macronutrient in the diet remains to be elucidated. Male C57BL/6 mice were fed with: control (CD), CD and sweetened condensed milk (HS), high-fat (HF), and HF and condensed milk (HSHF). After 2 months, increased body weight, glucose intolerance, adipocyte size and cholesterol levels were observed. As compared with CD, HS ingested the same amount of calories whereas HF and HSHF ingested less. HS had increased plasma AST activity and liver type I collagen. HF caused mild liver steatosis and hepatocellular damage. HF and HSHF increased LDL-cholesterol, hepatocyte and adipocyte hypertrophy, TNF-α by macrophages and decreased lipogenesis and adiponectin in adipose tissue (AT). HSHF exacerbated these effects, increasing IR, lipolysis, mRNA expression of F4/80 and leptin in AT, Tlr-4 in soleus muscle and IL-6, IL-1ß, VCAM-1, and ICAM-1 protein in AT. The three obesogenic diets induced obesity and metabolic dysfunction. HS was more proinflammatory than the HF and induced hepatic fibrosis. The HF was more detrimental in terms of insulin sensitivity, and it caused liver steatosis. The combination HSHF exacerbated the effects of each separately on insulin resistance and AT inflammatory state.
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Dieta Hiperlipídica , Inflamação/etiologia , Resistência à Insulina , Leite , Obesidade/etiologia , Adipócitos/metabolismo , Animais , Mediadores da Inflamação/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Edulcorantes/administração & dosagemRESUMO
UNLABELLED: The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. OBJECTIVES: The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. MATERIAL AND METHODS: The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. RESULTS: The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. CONCLUSIONS: Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs.
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Cartilagem Articular/metabolismo , Côndilo Mandibular/metabolismo , Deficiência de Proteína/metabolismo , Receptor de Insulina/metabolismo , Animais , Cartilagem Articular/citologia , Contagem de Células , Condrócitos/fisiologia , Colágeno/análise , Feminino , Imuno-Histoquímica , Masculino , Côndilo Mandibular/citologia , Microscopia Eletrônica de Varredura , Ratos Wistar , Receptor de Insulina/análise , Fatores de TempoRESUMO
The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .
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Animais , Camundongos , Anti-Inflamatórios não Esteroides/metabolismo , Ciclo-Oxigenase 1/metabolismo , /metabolismo , Inibidores de Ciclo-Oxigenase/metabolismo , Piroxicam/análogos & derivados , Tiazinas/metabolismo , Tiazóis/metabolismo , Substituição de Aminoácidos , Anti-Inflamatórios não Esteroides/química , Arginina/química , Arginina/genética , Arginina/metabolismo , Sítios de Ligação , Domínio Catalítico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/genética , /química , /genética , Inibidores de Ciclo-Oxigenase/química , Ligação de Hidrogênio , Leucina/química , Leucina/genética , Leucina/metabolismo , Mutação , Piroxicam/química , Piroxicam/metabolismo , Estrutura Secundária de Proteína , Serina/química , Serina/genética , Serina/metabolismo , Tiazinas/química , Tiazóis/química , Tirosina/química , Tirosina/genética , Tirosina/metabolismo , ÁguaRESUMO
O século XX foi caracterizado pelo aumento na longevidade do ser humano, sendo que a expectativa de vida equivale a quase o dobro da idade alcançada no início do século. O envelhecimento é um processo progressivo e inevitável que ocorre com o avanço da idade, independentemente de doença, estilo de vida ou fatores ambientais. Está acompanhado de modificações morfofisiológicas que determinam à perda gradual da capacidade de adaptação do indíviduo ao meio ambiente. No trato gastrointestinal (TGI), o processo de envelhecimento pode provocar alterações morfofuncionais significativas nos plexos entéricos, ocasionando maior incidência de processos patológicos. A regulação da motilidade do TGI é controlada principalmente pelos neurônios mioentéricos e alterações na densidade destes neurônios podem resultar em modificações na freqüência e amplitude da contração intestinal. Dessa forma, este trabalho teve como objetivo avaliar a densidade dos neurônios mioentéricos NADPH-diaforase positivos do duodeno de ratos Wistar durante o processo de envelhecimento. Para tanto, foram utilizados 15 ratos machos da linhagem Wistar, divididos em três grupos (n=5/grupo): C6 (animais com seis meses de idade); C12 (animais com doze meses de idade); C18 (animais de dezoito meses). Os animais dos grupos C12 e C18 aos seis meses de idade foram transferidos para o biotério setorial, onde permaneceram até aos 12 e 18 meses respectivamente, sob condições ambientais controladas de temperatura e de iluminação e água ad libitum. Após o período experimental todos os animais foram submetidos a eutanásia e os duodenos foram coletados e processados pela técnica histoquímica da NADPH-diaforase. Ao compararmos os grupos C6, C12 e C18 verificou-se uma diminuição na densidade neuronal (número de neurônios/mm²) com o envelhecimento, entretanto esta diferença só foi significativa (p<0,05) nos animais com 18 meses de idade. Essa redução na densidade de neurônio nitrérgicos também foi relatada na literatura no duodeno e em outros segmentos intestinais, em diferentes espécies animais com o avanço da idade. Tendo em vista tais alterações, se faz necessário o desenvolvimento de intervenções terapêuticas, que visem minimizar os efeitos do envelhecimento, melhorando desta forma a qualidade de vida da população idosa.
The twentieth century was characterized by increasing in human longevity, being life expectancy equivalent to practically twice of the age reached at the beginning of the century. The aging is a progressive and inevitable process that occurs with age and does not depend of diseases, lifestyle or environmental factors; it is accompanied by morph physiological changes that determine the progressive loss of individual´s ability to adapt to the environment. In the Gastrointestinal Tract (GIT), the aging process can provoke significant morpho functional changes in the enteric plexuses causing higher incidence of pathological processes. The GIT motility is primarily controlled by myenteric neurons, thus, changes in the density of these neurons may result in changes in the frequency and amplitude of intestinal contraction. Therefore, the aim of this work to evaluate the density of myenteric neurons NADPH-diaforase positive in the duodenum of Wistar rats during aging process. Fifteen male wistar rats were used in the experiment. The animals were divided in three groups of five animals (n=5) as following: C6 (animals aged six months); C12 (animals aged twelve months); C18 (animals aged eighteen months). The animals from the groups C12 and C18 were previously transferred to vivarium, under environmental conditions of controlled temperature and light and water ad libitum, since have reached six months to twelve and eighteen months respectively. After experimental period, all animals were euthanized and the duodenum were collected and processed for standard histochemical NADPH-diaforase technique. As a result, a decrease in the neuronal density (mm²) at the time with aging was observed in the three groups, C6, C12 and C18, however, this difference was remarkable (p>0,05) from twelve months old. This reduction in the density of nitrergic neurons was previously reported in the duodenum and other intestinal segments of different animals under aging process. Based in such alterations, were believed that there is a need of the development of therapies that minimize the effects of aging, thus, improving the quality of elderly life.