肠脑轴参与动物食欲的调节机制

肠脑轴是由中枢系统、胃肠道系统共同构成的双向通信系统,其主要通过下丘脑食欲中枢和胃肠道食欲激素来调节动物的食欲,控制其体重,参与能量稳态的调节,是研究动物肥胖和2型糖尿病等代谢疾病的重要轴系.本文综述了肠脑轴对动物食欲、能量平衡和体重的调节作用,展望了肠脑轴在肥胖等相关代谢疾病治疗中的研究前景.     

Interhemispheric asymmetry and the typological characteristics of the nervous system in rats

The paper is devoted to studies of interrelations between behavioural dominance of the left or right hemisphere and typological characteristics of the nervous system in rats. Rats with a strong type of nervous system are shown to possess species-specific interhemispheric asymmetry. In animals with a balanced nervous system it is greater than in animals with an unbalanced nervous system. Rats with a weak type of nervous system have no species-specific interhemispheric asymmetry.     

Effect of peripheral ethanol metabolism on the central nervous system.

The main symptoms of ethanol intoxication, tolerance, and physical dependence presumably, derive from the effects of ethanol on the central nervous system. It is not known clearly how and to what extent these effects are caused by ethanol itself or by its metabolic derivatives, chiefly acetaldehyde, formed in the liver, and transported into the brain through the blood stream. Since the concentrations of acetaldehyde found in the blood and brain of human subjects and experimental animals are approximately 44 times lower than the lowest effective concentrations found in in vitro experiments, it remains to be established whether acetaldehyde derived under in vivo conditions from the oxidation of ethanol in the liver plays any significant role in suppressing the respiratory metabolism or other metabolic pathways in the brain. It is concluded that the site of ethanol effects on the central nervous system is probably associated with that part of the metabolic system that is dependent on normal functioning of the neuronal cell membrane and probably has little relation to the peripheral or central metabolism of ethanol.     

The relation of the typological classification of dogs to their behavioral characteristics in variations between the probability and the value of reinforcement]

In studying of dogs behaviour in coordinates system "Requirements and probability of their satisfaction" it has been established that selection of behaviour strategy is closely connected with individual typological properties of animals. In experiments with equally-probable alimentary reinforcement a direct correlation was found between the strength parameter of the nervous system and the strategy of dogs behaviour. Animals of strong types manifested the character of reaction which consisted in determination and goal-directedness, while the animals of the weak type manifested other character, having features of uncertainty, indefinition, hesitations. In conditions of conflict between probability and value of reinforcement the dogs manifested two opposite strategies of behaviour: orientation to highly probable events (choleric and phlegmatic) and to low-probable events (sanguinic and melancholic) what is connected with individual properties of functioning and the character of interaction of four brain structures (frontal cortex, hippocampus, hypothalamus, amygdala).     

Evolutionary origin of autonomic regulation of physiological activities in vertebrate phyla

Proper regulation of physiological activities is crucial for homeostasis in animals. Autonomic regulation of these activities is most developed in mammals, in which a part of peripheral nervous system, termed the autonomic nervous system plays the dominant role. Circulatory activity and digestive activity in vertebrates change in opposite phases to each other. The stage where circulatory activity is high and digestive activity is low is termed the "fight or flight stage" while the stage where circulatory activity is low and digestive activity is high is termed the "rest and digest stage". It has been thought that the autonomic nervous system originated in early vertebrate phyla and developed to its greatest extent in mammals. In this study, we compared the pattern of change of circulatory and digestive activities in several invertebrates and found that the two stages seen in mammals are also present in a wide variety of animals, including evolutionarily early-diverging invertebrate taxa. From this and other arguments we propose a novel possibility that the basic properties of the autonomic nervous system were established very early in metazoan evolution.     

The expression of TGFbeta signal transducers in the hypodermis regulates body size in C. elegans

In C. elegans, a TGFbeta-related signaling pathway regulates body size. Loss of function of the signaling ligand (dbl-1), receptors (daf-4 and sma-6) or Smads (sma-2, sma-3 and sma-4) results in viable, but smaller animals because of a reduction in postembryonic growth. We have investigated the tissue specificity of this pathway in body size regulation. We show that different tissues are reduced in size by different proportions, with hypodermal blast cell size most closely proportional to body size. We show that SMA-3 Smad is expressed in pharynx, intestine and hypodermis, as has been previously reported for the type I receptor SMA-6. Furthermore, we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity. Interestingly, SMA-3 protein accumulation was found to be negatively regulated by the level of Sma/Mab pathway activity. Using genetic mosaic analysis and directed expression of SMA-3, we find that SMA-3 activity in the hypodermis is necessary and sufficient for normal body size. As dbl-1 is expressed primarily in the nervous system, these results suggest a model in which postembryonic growth of hypodermal cells is regulated by TGFbeta-related signaling from the nervous system to the hypodermis.     

A comparative study on the influence of cysteamine and metyrapone on mixed-function oxygenase activities in variously pretreated liver microsomes from rats and mice.

It has been found that metyrapone can inhibit both type I and type II mixed-function oxygenase reactions, while cysteamine inhibits only type I activity in this mammalian system. Following pretreatment with phenobarbital and 3-methylcholanthrene the half-maximal inhibiting concentrations for the O-demethylation of paranitranisol are increased for cysteamine and decreased for metyrapone. Both cysteamine and metyrapone give type II binding spectra with oxidized cytochrome P-450. The negative and positive peaks are at 393 and 426 nm respectively for metyrapone, and 410 and 434 nm for cysteamine. Cysteamine showed no binding comparable to that of metyrapone for reduced cytochrome P-450. Metyrapone showed little or no inhibition of the NADH cytochrome-c reductase (EC 1.6.1.1) or NADPH (EC 1.6.2.3) cytochrome-c reductase while cysteamine had a more or less strong inhibiting effect depending on the pretreatment of animals. Neither the binding to P-450 heme nor the inhibition of NADH and NADPH cytochrome-c reductase correlates well with cysteamine inhibition of total activity. It is therefore suggested that cysteamine reacts with an intermediate electron carrier of non-heme iron or glycoprotein character thus inhibiting mixed-function oxygenase activity.     

Antioxidative protection in the central nervous ganglia of a mollusc Lymnaea stagnalis at modulation of activity of the NO-ergic system

In experiments on molluscs Lymnnaea stagnalis the state of antioxidative protection is studied in central nervous ganglia during a long-term activation (inhibition) of synthesis of nitric monoxide (NO) in the body. Effect of the blocker of NO-synthase N(G)-nitro-L-arginine (L-NNA) at the background of enhancement of pulmonary respiration has been established to be associated with a rise of levels of reduced glutathione and TBK-active products in the nervous tissue at preservation of a relatively high superoxide dismutase activity and a low glutathione peroxidase activity as compared with control group and the animals treated with the metabolic precursor of NO synthesis L-arginine. In spite of the revealed disturbances of balance of the body pro- and antioxidative system, DNA electrophoresis detected no products of its degradation, which can indicate the absence of massive programmed death of the nervous tissue cells in Lymnaea stagnalis during modulation of activity of the NO-ergic system.     

Individual sensitivity of Wistar rats to piracetam

Effects of repeated piracetam (PIR) injections in a dose of 40 and 250 mg/kg/day on the learning in Water rats were studied. It has been found that character of the effects depends on typological features of the animals. Rats with strong predominance of excitation (choleric type) showed low sensitivity to PIR. Small dose of PIR provoked clear negative effect in rats with relative balance of the basic nervous processes: excitation and inhibition (sanguine and phlegmatic types). Despite of expressed activation of associative process, it complicated integrative activity. Small dose of PIR showed anxiolytic and psycho-stimulant actions only in initially unlearned rats characterized by high level of fear. Large dose of PIR had negative influence on the learning process in all animals, irrespective of typological features. Thus, the results of this study allow to suppose that the individual sensitivity of an animal to action of a pharmacological medication is caused by morpho-functional and neurochemical intraspecific heterogeneity.     

Body weight and metabolic level in growing chickens

Body weight and metabolic level in growing chickens. Acta Physiol. Pol., 1977, 28 (6): 575-583. In the investigations carried out on 128 White Rock chicken the metabolic level was determined under standard conditions in chickens characterising by different growth rate resulted from different feeding levels. It was shown that the feeding level of growing chicken has an essential influence on the character of the regression between the metabolic level and body weight. It was also found that this regression is not necessarily ot the character of Kleiber's function H = aWb. The differences in the metabolic level between the chickens maintained on different feeding levels did not disappear even after 4 days of starvation. In the light of the obtained results and recent investigations by other authors the usefulness of the so-called metabolic unit of the body size based on W0.75 in context to growing animals within one species has bee criticized.     

Postnatal development of rat heart during 6-hydroxydopamine or propranolol treatment

Progressive postbirth development of mammalian heart contractile function is accompanied by augmentations of aerobic metabolic potential and cardiac myofibrillar ATPase activity. The temporal similarity of the above developmental sequences suggested that a single, unifying factor may coordinate myocardial maturation. It was hypothesized that cardiac sympathetic nervous system development might be regulating other aspects of myocardial growth. To test this hypothesis, previously well-defined aspects of heart metabolism and contractile protein ATPase activity were determined in rats which were either sympathectomized with 6-hydroxydopamine (6-OHDA) or subjected to chronic, beta-adrenergic blockade (propranolol) throughout the postbirth period from 3 to 6 weeks of age. Neither 6-OHDA treatment nor chronic, beta-adrenergic blockade resulted in a significant reduction of any metabolic enzyme specific activity or in myofibrillar ATPase. Myofibrillar creatine phosphokinase (CPK) activity underwent greater enhancement relative to ATPase during normal heart growth. Significant and divergent influences were exerted by 6-OHDA and propranolol drug regimens on myofibrillar CPK/ATPase enzyme activity ratio. These results indicate (a) the potential for independent regulation of myofibrillar CPK and ATPase, and (b) the advisability of evaluating CPK, ATPase, and CPK/ATPase enzymatic activities as myofibrillar correlates of heart contractile function. Nevertheless, the majority of developmentally related processes in the heart are minimally influenced by chemical sympathectomy.     

The role of neuromediators and proteins in genetic and functional organization of animal brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow determination of individual behavioral features and estimation of individual brain structures in these processes.     

Modes of metabolic compensation during mitochondrial disease using the Drosophila model of ATP6 dysfunction

Numerous mitochondrial DNA mutations cause mitochondrial encephalomyopathy: a collection of related diseases for which there exists no effective treatment. Mitochondrial encephalomyopathies are complex multisystem diseases that exhibit a relentless progression of severity, making them both difficult to treat and study. The pathogenic and compensatory metabolic changes that are associated with chronic mitochondrial dysfunction are not well understood. The Drosophila ATP6(1) mutant models human mitochondrial encephalomyopathy and allows the study of metabolic changes and compensation that occur throughout the lifetime of an affected animal. ATP6(1)animals have a nearly complete loss of ATP synthase activity and an acute bioenergetic deficit when they are asymptomatic, but surprisingly we discovered no chronic bioenergetic deficit in these animals during their symptomatic period. Our data demonstrate dynamic metabolic compensatory mechanisms that sustain normal energy availability and activity despite chronic mitochondrial complex V dysfunction resulting from an endogenous mutation in the mitochondrial DNA. ATP6(1)animals compensate for their loss of oxidative phosphorylation through increases in glycolytic flux, ketogenesis and Kreb's cycle activity early during pathogenesis. However, succinate dehydrogenase activity is reduced and mitochondrial supercomplex formation is severely disrupted contributing to the pathogenesis seen in ATP6(1) animals. These studies demonstrate the dynamic nature of metabolic compensatory mechanisms and emphasize the need for time course studies in tractable animal systems to elucidate disease pathogenesis and novel therapeutic avenues.     

Individual typological characteristics of hormonal responses in dogs during psychoemotional stress

Effects of psycho-emotional stress on contents of steroid hormones in the blood were studied in dogs with different typological properties of the higher nervous activity. Under stress condition, a significant correlation between the cortisol and testosterone levels and the dogs' typological characteristics was found. The more obvious fluctuations in the hormones level occurred in animals with strong and excitable type of the nervous system as compared with dogs belonging to weak and inert type.     

Role of autonomic nervous system on heart rate in experimental hypertension

Heart rate and the role of the autonomic nervous system in hypertensive conscious rats by subtotal nephrectomy were studied. Heart rate is significantly higher in the hypertensive rats. Sympathetic blockade with an intravenous injection of propranolol produces a higher decrease in heart rate of hypertensive rats than in control rats. Intravenous injection of atropine produces an increase in heart rate in both groups of animals. It is significantly higher in the control rats than in hypertensive animals. When the autonomic nervous system is blocked with atropine and propranolol, intrinsic heart rate is similar in both groups of animals. Similar results are obtained after blocking ganglionic transmission with hexamethonium. No significative differences are observed in heart rate after intracerebroventricular injection of hemicholinium-3 between both groups of rats. Results show an increased cardiac sympathetic tone, reduced parasympathetic activities, no alterations in the pacemaker activity and implications of central acetylcholine. These alterations in the autonomic nervous system have an important role in the maintenance of elevated heart rate in this experimental model of arterial hypertension.     

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

To assess the importance of the sympathetic nervous system in regulating body weight during prolonged leptin infusion, we evaluated food intake, body weight, and physical activity in conscious, unrestrained rats. Initial studies illustrated that prolonged intracerebroventricular (ICV) infusion of leptin enhanced substrate oxidation so that adipose tissue lipid stores were completely ablated, and muscle triglyceride and liver glycogen stores were depleted. After neonatal chemical sympathectomy, changes in weight and food intake were compared in groups of sympathectomized (SYM) and control (CON) adult animals during ICV infusion of leptin. CON animals lost 60 +/- 9 g over 10 days vs. 25 +/- 3 g in the SYM animals when food intake was matched between the two groups. Greater weight loss despite similar energy intake points to an important role of the sympathetic nervous system in stimulating energy expenditure during ICV leptin infusion by increasing the resting metabolic rate, since no differences in physical activity were observed between CON and SYM groups. In conclusion, activation of the SNS by leptin increases energy expenditure by augmenting the resting metabolic rate.     

Effects of electromagnetic field of thermal intensity on the hypophysis-thyroid unit of the neuroendocrine system

Acute 12-minute exposure of laboratory rats to microwaves with specific dose rate (SAR) of 30 W/kg that exceeded a basal metabolism caused a transient response of hyppophysis-thyroid system of compensatory-adaptive character. Prolonged exposure to microwaves of less intensity (SAR = 6 W/kg, which approximately corresponds to basic metabolic rate for these animals) caused insufficiency of the function of thyroid control in a form of primary hypothyroidis.     

Electroencephalographic characteristics in animals with different typologic characteristics of their higher nervous activity]

Manifestation of typological characteristics of higher nervous activity in EEG energo-(amplitude-) frequency parameters were studied in chronic experiments on cats in a state of rest. EEG Of the animals of a strong nervous system type were characterized by a comparatively steady prevalence of alpha-activity and a stable relationship between the summary energy parameters of the basic frequencies. The brain electrical activity of cats with a weak type of higher nervous activity was in some cases characterized by instability of the general pattern: the summary parameter of each rhythm often changed, while at different intervals of time any of them could be recorded as predominant; in other cases slow waves were steadily prominent, and the summary energy of alpha-activity was low.     

The Role of Neurotransmitters and Proteins in the Genetic-Functional Organization of the Animal Brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (the hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow the determination of individual behavioral features and an estimation of individual brain structures in these processes.     

Characteristics of biochemical processes of the liver in rats with various types of open-field behavior

Respiration and phosphorylation of liver mitochondria, lipid spectrum of the blood serum activity of hepatocytes main microsomal enzymes were studied in outbred rats with various emotionality. It was found that in low-emotional rats, the intensity of phosphorylation processes in liver mitochondria and enzymes activity of hematocytes microsomal oxidative system responsible for detoxication processes,-- was significantly higher than in low-emotional animals. Analogous differences were found in the lipid blood spectrum and in liver mitochondria antioxidant activity of animals with different emotionality. It is supposed that there is an inter-connection between animals behaviour in the open field and the character of biochemical processes in the liver.