Relations of neuropeptide Y and heme oxygenase-1 expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy

Abstract Purpose: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. Results: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). Conclusion: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.

Associação de POMC, NPY e IRS2 hipotalâmicos com padrões de comportamento alimentar em ratos Wistar normais e sobrepeso / Association of POMC, NPY and hypothalamic IRS2 with patterns of eating behavior in overweight and normal Wistar rats

O comportamento alimentar de uma espécie é determinado por um conjunto de características filogenéticas, ontogenéticas, e epigenéticas, e regulado por fatores internos e externos ao organismo. Os fenômenos naturais que regem a vida no nosso planeta são periódicos em sua maioria, e a oferta de alimentos não é exceção. Cada safra é seguida de uma entressafra, e este ritmo sincroniza diversos outros ritmos, exógenos e endógenos, capazes de determinar a sobrevivência de espécies. Uma das estratégias adaptativas mais primitivas e bem sucedidas na dinâmica oscilatória da natureza, é o acúmulo de reservas. Nossa espécie, nos últimos 50 anos, vive uma situação de grande oferta de alimentos, período este extremamente pequeno, se visto sob a ordem de grandeza da evolução humana. Este fenômeno tem sido determinante na prevalência do depósito de energia e em decorrência, do surgimento da obesidade e suas consequentes patologias. O hipotálamo está intimamente associado à homeostase energética e ao comportamento alimentar. No núcleo arqueado hipotalâmico encontram-se populações neuronais orexigênicas e anorexigênicas, dentre as quais, as que expressam os neuroreceptores POMC, NPY e o substrato de receptor de insulina IRS2. A modificação da expressão destas proteínas tem sido associada à alterações do comportamento alimentar, bem como à impressão e programação metabólica, capazes de induzir obesidade em ratos adultos. A correlação desta circuitaria neuronal com o comportamento alimentar, porém, ainda não está suficientemente compreendida. A detecção do estado de fome-saciedade nos ratos, fundamental no estudo da neurofisiologia relacionada ao comportamento alimentar, vem sendo obtida via de regra, por meio de procedimentos complexos de observação comportamental. O presente estudo contribui para o conhecimento de padrões de alimentação determinados por condições nutricionais, e sua relação com a expressão neurofisiológica hipotalâmica dos neurônios POMC, NPY e IRS2 ...

The feeding behavior of a specie is determined by a group of phylogenetic, ontogenetic, and epigenetic features, and regulated by internal and external factors to the organism. The natura phenomena that govern life in our planet are mainly periodic, and the food stocks is not an exception. Each harvest is followed by a time between harvests, and this rhythm synchronizes other several exogenous and endogenous rhythms, capable of determining the survival of species. One of the most primitive strategies of adaptative evolution of species, and what usually happens regarding the oscillatory dynamics of nature, is the reserve accumulation. Our species, in the last 50 years, has been living a situation of great food offer, such period is exremely small if analysed under the greatness order of the human evolution. This phenomenon has been decisive in the prevalence of the energy deposit and, in consequence, determining the appearance of obesity and its consequent pathologies. The hypothalamus is intimately associated to the energy homeostasis and the feeding behavior. In the arcuate nucleous are orexigenic and anorexigenic neuronal populations, that express the neuroreceptors POMC, NPY and insulin receptor substratum IRS2. The modification of these proteins expression, has been associated to alterations of the feeding behavior, as well as to the metabolic imprinting and programming, capable to induce obesity in adult rats. The correlation of this neuronal circuits with the alimentary behavior, however, it is not yet sufficiently understood. The detection of the hunger-satiation state in the rat, crucial in the neurophysiology studies related to the alimentary behavior, has been obtained through complex procedures of behavioral observation. The present study contributed to the knowledge of certain feeding patterns for nutritional conditions, and its relationship with the neurophysiological expression of POMC, NPY and IRS2 neurons. Using the metabolic programming ...

Programação do processo fome-saciedade de animais desnutridos no início da lactação: papel do NPY/AgRP e POMC / Programming hunger-satiety process of malnourished animals in early lactation: role of NPY/AgRP and POMC

A modulação do processo fome-saciedade é um fator determinante para o crescimento normal dos sistemas metabólicos. Tem sido demonstrado que variações nutricionais nos períodos pré e pós-natal induzem modificações nas projeções e/ou contatos dos circuitos neuronais hipotalâmicos, gerando uma "reprogramação" deste sistema que envolve mecanismos de interação da ação primária de hormônios como leptina em neurônios orexigênico (NPY/AgRP) anorexigênicos (POMC) no núcleo arqueado, para regular o comportamento alimentar. O objetivo deste trabalho foi estudar a programação do processo fome-saciedade no núcleo arqueado hipotalâmico, em curto e longo prazos, em animais que foram desnutridos no início da lactação. Para isso, utilizamos ratos Wister desnutridos nos primeiros 10 dias de lactação com a utilização de dieta materna com 0% de proteína e que foram submetidos a novo período de desnutrição protéica na fase adulta (60 dias de idade) por 3 dias. Para o estudo do processo fome-saciedade, as variáveis avaliadas foram peso corporal, razão peso corporal / consumo alimentar, conteúdos de receptores de leptina (Ob-Rb) e de neuropeptídeos hipotalâmicos (NPY/AgRP e POMC). Observamos que ao final de 10 dias de desnutrição na lactação, os animais desnutridos apresentaram menor peso corporal (FD - fêmea desnutrida, 50% e MD - macho desnutrido, 53%) e aumento dos conteúdos de Ob-Rb (FD: 121,67% e MD: 132,73%), NPY/AgRP (FD: 32,31% e MD: 115,62%) e POMC (FD: 71,2% e MD: 26,58%). Aos 60 dias de vida, os animais desnutridos apresentaram maior razão peso corporal / consumo alimentar e não evidenciamos diferença nos conteúdos de Ob-Rb, NPY/AgRP e POMC (p<-0,05). Aos 63 dias de vida, fêmeas (FDD) e machos desnutridos (MDD), após um segundo episódio de desnutrição, apresentaram redução de peso corporal (FDD: 12,4% e MDD: 10,75%) e consumo alimentar (FDD: 57,5% e MDD: 39,88%). O conteúdo dos neuropeptídeos orexigênicos (NPY/AgRP)...

The modulation of the hunger-satiety process is a determining factor for the normal growth of the metabolic systems. It has been demonstrated that nutritional variations during pre- and postnatal lead to modifications in projetions and/or contacts of hypothalamic neuronal circuits generating a "reprogramation" of this system, which involves mechanisms of interation of primary action of hormone as leptin in NPY/AgRP and POMC neurons in the arcuate nucleus, to regulate eating behavior. Our aim was to study the programation in the hunger-satiety process in the arcuate nucleus, in the short and long terms, in animals that were malnourished during the early lactation period. In the present study we used Wistar rats that were malnourished during the first 10 days of lactation (0% protein maternal diet) and that were submitted to new a period of malnutrition at adulthood (60 days-old) for 3 days. To study the hunger-satiety process, the variables evaluated were: body weight, body weight/food intake ratio, hypothalamic content of the leptin receptor (Ob-Rb) and the orexigenic NPY/AgRP and anorexigenic POMC neuropeptides. We observed at the end of 10 days of malnutrition during lactation, that the malnourished animals had lower body weight (MF - malnourished female, 50% and MM - malnourished male, 53%) and higher content of Ob-Rb (MF: 121,67% and MM: 132,73%), NPY/AgRP (MF: 32,31% e MM: 115,62%) and POMC (MF: 71,2% e MM: 26,58%). At 60 days, the malnourished animals had higher body weight/food intake ratio and showed no change in the Ob-Rb, NPY/AgRP and POMC content (p<-0,05). At 63 days of life, malnourished female and male after a second episode of malnutrition, had lower body weight (MMF: 12,4% and MMM: 10,75%) and food intake (MMF: 57,5% and MMM: 39,88%). The content of neuropeptides (NPY/AgRP) was significantly lower (MMF: 22,6% and MMM: 26,58%), while the content of Ob-Rb (MMF: 92,27% and MMM: 28%) and POMC neuropeptide (MMF: 22,34% and MMM:27,27%)...

Tabagismo e variação ponderal: a fisiopatologia e genética podem explicar esta associação?: [revisão] / Smoking and changes in body weight: can physiopathology and genetics explain this association?: [review]

O tabagismo é a principal causa de morte prevenível na maioria dos países, inclusive no Brasil. Parar de fumar é uma estratégia importante para reduzir a morbidade e mortalidade associada às doenças tabaco-relacionadas. Sabe-se da relação inversa entre uso de nicotina e peso corporal, onde o índice de massa corporal tende a ser menor em fumantes quando comparados aos não fumantes. Além disso, abstinência tabágica resulta em aumento de peso, sendo que ex-fumantes geralmente aumentam de 5 a 6 kg, mas cerca de 10 por cento adquirem mais de 10 kg. O tratamento farmacológico para a cessação do tabagismo pode atenuar este ganho de peso. O aumento de peso na cessação do tabagismo como contributório à epidemia de obesidade é pouco estudado. Nos EUA, calcula-se que a fração do problema atribuível à cessação do tabagismo seja de 6 por cento para homens e 3,2 por cento para mulheres. Os mecanismos não são claros, mas há evidências mostrando que a dopamina e serotonina diminuem a ingestão alimentar. A administração de nicotina por qualquer via eleva agudamente os níveis destes neurotransmissores no cérebro, causando menor necessidade de ingestão energética e diminuindo o apetite. Além disso, a nicotina tem efeito direto no metabolismo do tecido adiposo, influenciando a taxa de ganho ponderal após a cessação do tabagismo. A leptina, grelina e neuropeptídio Y são peptídeos que podem contribuir para esta relação inversa entre nicotina e índice de massa corporal, em um papel ainda não determinado como conseqüente ou causador das variações ponderais.

Tobacco use is the leading preventable cause of death in most countries, including Brazil. Smoking cessation is an important strategy for reducing the morbidity and mortality associated with tobacco-related diseases. An inverse relationship between nicotine use and body weight has been reported, in which body weight tends to be lower among smokers than among nonsmokers. Smoking abstinence results in an increase in body weight for both males and females. On average, sustained quitters gain from 5 to 6 kg, although approximately 10 percent gain more than 10 kg. Pharmacological treatment for smoking cessation attenuates weight gain. The importance of smoking cessation as a contributing cause of the current obesity epidemic has been little studied. In the USA, the rate of obesity attributable to smoking cessation has been estimated at approximately 6.0 and 3.2 percent for males and females, respectively. Although the mechanisms are unclear, there is evidence that dopamine and serotonin are appetite suppressants. The administration of nicotine, regardless of the delivery system, acutely raises the levels of these neurotransmitters in the brain, reducing the need for energy intake and consequently suppressing appetite. In addition, nicotine has a direct effect on adipose tissue metabolism, influencing the rate of weight gain following smoking cessation. Leptin, ghrelin and neuropeptide Y are substances that might constitute factors involved in the inverse relationship between nicotine and body mass index, although their roles as determinants or consequences of this relationship have yet to be determined.

Changes in orexin-A and neuropeptide Y expression in the hypothalamus of the fasted and high-fat diet fed rats

This study was aimed to investigate the changes of orexin-A (OXA) and neuropeptide Y (NPY) expression in the hypothalamus of the fasted and high-fat diet fed rats. For the experiments, the male Sprague-Dawley (SD) rats were used as the model of high-fat diet-induced obesity. The mean loss of body weight (MLBW) did not show the linear pattern during the fasting; from 24 h to 84 h of fastings, the MLBW was not significantly changed. The numbers of OXA-immunoreactive (IR) neurons were decreased at 84 h of fasting compared with those in other five fasting subgroups. The NPY immunoreactivities in the arcuate nucleus (ARC) and the suprachiasmatic nucleus (SCN) observed at 84 h of fasting were higher than that observed at 24 h of fasting. The number of OXA-IR neurons of the LHA (lateral hypothalamic area) in the high-fat (HF) diet fed group was more increased than that of the same area in the normal-fat (NF) diet fed group. The NPY immunoreactivities of the ARC and the SCN were higher in HF group than those observed in the same areas of NF group. Based on these results, it is noteworthy that the decrease of the body weight during the fast was not proportionate to the time-course, implicating a possible adaptation of the body for survival against starvation. The HF diet might activate the OXA and the NPY in the LHA to enhance food intake.

A quantitative analysis of peptidergic innervation in sinoatrial node in cases of sudden manhood death syndrome / 法医学杂志

OBJECTIVE@#To study the distribution and proportion of neuropeptide containing nervers in the sinus node in cases of sudden manhood death syndrome (SMDS) and to explore the mechanism of SMDS.@*METHODS@#Immunohistochemical staining and quantitative analysis of neuropeptide Y (NPY) and vasoactive intestinal peptide(VIP) in the sinus node in 6 cases of SMDS and in 12 cases of non-cardiac death(control group) were achieved by LSAB method and computerized image system.@*RESULTS@#As for NPY positive materials, VIP positive materials and the ratio of VIP/NPY in the sinus nodes, there were no significant difference between the control group and SMDS group.@*CONCLUSION@#The mechanism of SMDS and the abnormality of autonomic nervous innervation in the sinoatrial nodes maybe incorrelation.

Neuropeptide control of the cardiovascular system in fish and reptiles

Accumulating evidence shows the involvement of neuropeptides in cardiovascular control in mammals as well as non-mammalian species. Our own immunohistochemical studies indicate a sparse innervation only in cyclostomes, holostean fish and lungfish, a more extensive variation and distribution in elasmobranchs and teleosts, and a rich and varied innervation of the cardiovascular system in crocodiles and lizards. Vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), gastrin releasing peptide (GRP) and tachykinins are present in most vertebrate groups. VIP is vasodilatory in the Atlantic cod (Gadus morhua) as in most mammalian species, but increases gut vascular resistance in the spiny dogfish (Squalus acanthias). NPY potentiates the effect of noradrenaline on skate (Raja rhina) coronary vessels, suggesting an interaction between adrenergic mechanisms and NPY early in evolution, but studies in the spiny dogfish and the crocodile also demonstrate different mechanisms for the action of NPY and adrenaline in some species. Bombesin/GRP increases flow to the gut in the spiny dogfish by an increase in somatic vascular resistance, while visceral resistance remains unchanged. In the caiman (Caiman crocodylus crocodylus) bombesin causes a shunting of blood from the lung to the gut. Substance P and other tachykinins in general increase flow to the gut, and on some occasions also increase somatic blood flow. Flow in the anastomosis of the crocodile (Crocodylus porosus) gut is increased by substance P. The results presented here are a review of several published and unpublished studies.

Efferent projections of the pigeon intergeniculate leaflet containing neuropeptide Y

The present study was performed to map efferent projections of the pigeon intergeniculate leaflet (IGL) to other visual structures, with emphasis on the pathways containing neuropeptide Y (NPY). After injections of an anterograde tracer (Phaseolus vulgaris leucoagglutinin) into the IGL, labeled axons and presumptive terminals were seen in several retinorecipient and visually-related nuclei. All such areas contained immunoreactive fibers to antibodies against NPY. Electrolytic lesion of the IGL provoked a marked reduction in the number of NPY-labeled fibers in these visual structures. The data suggest that the IGL is the source of NPY-labeles axons which occur in many visual nuclei of the pigeon brain