It has been suggested that thiazolidinediones (TZDs) ameliorate insulin resistance in muscle tissue by suppressing muscle lipid storage and the activity of novel protein kinase C (nPKC) isoforms. To test this hypothesis, we analyzed long-term metabolic effects of pioglitazone and the activation of nPKC-ε and -θ isoforms in an animal model of the metabolic syndrome, the spontaneously hypertensive rat (a congenic SHR strain with wild type Cd36 gene) fed a diet with 60 % sucrose from the age of 4 to 8 months. Compared to untreated controls, pioglitazone treatment was associated with significantly increased basal (809±36 vs 527±47 nmol glucose/g/2h, P<0.005) and insulinstimulated glycogenesis (1321±62 vs 749±60 nmol glucose/g/2h, P<0.0001) in isolated gastrocnemius muscles despite increased concentrations of muscle triglycerides (3.83±0.33 vs 2.25±0.12 μmol/g, P<0.005). Pioglitazone-treated rats exhibited significantly increased membrane/total (cytosolic plus membrane) ratio of both PKC-ε and PKC-θ isoforms compared to untreated controls. These results suggest that amelioration of insulin resistance after long-term pioglitazone treatment is associated with increased activation of PKC-ε and -θ isoforms in spite of increased lipid concentration in skeletal muscles., I. Marková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The behavioural manipulation hypothesis posits that parasites can change the behaviour of hosts to increase the reproductive fitness of the parasite. The protozoan parasite Toxoplasma gondii fits this description well. Sexual reproduction occurs in the cat intestine, from which highly stable oocysts are excreted in faeces. Grazing animals, including rodents, can then ingest these oocysts. The parasite has evolved the capacity to abolish the innate fear that rodents have of the odours of cats, and to convert that fear into an attraction. This presumably increases the likelihood of the rodent being predated, thereby completing the parasite's life cycle. The behavioural syndrome produced by T. gondii does not have any precedent in neuroscience research. This is not a case where the normal functioning of fear system have been altered. This is not even the case of the altering of fear towards predator odours, while leaving other kinds of fear intact. This is an unprecedented example of one component of the fear being eliminated (and replaced by a novel attraction), while appearing to leave other domains unchanged. An understanding of the neurobiological effects of T. gondii is beginning to emerge. One possibility is T. gondii's preferential localisation to, and effects within the amygdala; this is particularly intriguing, given the role of this brain structure in the normal fear response. Obviously, far more must be understood, and the unique behavioural effects of T. gondii put very demanding constraints on any hypothesis we formulate to explain proximate neurobiological mechanisms.
The present study was aimed to investigate the mesenteric arteriovenous differences in blood glucose and lactate and plasma insulin in humans (n = 8) and rats (n=10). Arterial (abdominal aorta) and mesenteric vein blood glucose and lactate (enzymatic methods) and plasma insulin concentrations (radioimmunoassay) were measured in patients during abdominal surgery and in normal rats. Blood glucose levels were significantly (p<0.05) higher in the abdominal aorta than in the mesenteric vein in both rats (9.2±1.0 vs 7.5±0.8 mmol/1) and humans (10.4±2.9 vs 8.5±2.7 mmol/1). Blood lactate levels were higher (p<0.05) in the mesenteric vein in both rats (3.7±1.3 vs 2.8±0.9 mmol/1) and humans (0.7±0.23 vs 0.1 ±0.05 mmol/1). Plasma insulin concentrations were identical in the aorta or mesenteric vein in both rats (314.4± 162.0 vs 311.4±94.2 pmol/1) and humans (62.4±43.2 vs 61.8±48.0 pmol/1). In conclusion, both rat and human intestine retained a high proportion of arterially administered glucose and released lactate under the studied conditions.
b1_Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characte rized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that admi nistration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon an d other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomit ant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats., b2_However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA result s from both metabolic and nonmetabolic disturbances in these islets., T. Szkudelski, A. Zywert, K. Szkudelska., and Obsahuje bibliografii a bibliografické odkazy
Salusin-β is newly identified bioactive peptide of 20 amino acids, which is widely distributed in hematopoietic system, endocrine system, and the central nervous system (CNS). Although salusin- β extensively expressed in the CNS, the central cardiovascular functions of salusin-β are unclear. Our main objective was to determine the cardiovascular effect of microinjection of salusin-β into the nucleus tractus solitarii (NTS) in anesthetized rats. Bilateral or unilateral microinjection of salusin-β (0.94-94 μg/rat) into the NTS dose-dependently decreased blood pressure and heart rate. Bilateral NTS microinjection of salusin-β (9.4 μg/rat) did not alter baroreflex sensitivity. Prior application of the glutamate receptor antagonist kynurenic acid (0.19 μg/rat, n=9) into the NTS did not alter the salusin-β (9.4 μg/rat) induced hypotension and bradycardia. However, pretreatment with the GABA receptor agonist muscimol (0.5 ng/rat) within the rostral ventrolateral medulla (RVLM) completely abolished the hypotension (-14±5 vs. -3±5 mm Hg, P <0.05) and bradycardia (-22±6 vs. -6±5 bpm, P <0.05) evoked by intra-NTS salusin-β (9.4 μg/rat). In addition, we found that vagotomy didn’t influence the actions of salusin-β (9.4 μg/rat) in the NTS. In conclusion, our present study shows that microinjection of salusin-β into the NTS significantly produces hypotension and bradycardia, presumably by suppressing the activities of presympathetic neurons in the RVLM., Y. Lu, Y. S. Wu, D. S. Chen, M. M. Wang, W. Z. Wang, W. J. Yuan., and Obsahuje bibliografii
Models of basic types of epileptic seizures are elaborated not only in adult but also in immature rodents. It is important because at least half of human epilepsies starts during infancy and childhood. This paper presents a review of chemically and electrically induced models of generalized convulsive and nonconvulsive (absence) seizures as well as models of partial simple (neocortical) and complex (limbic) seizures in immature rats. These models can also serve as a tool for study the development of central nervous system and motor abilities because the level of maturation is reflected in seizure semiology. Age-dependent models of epileptic seizures (absences and flexion seizures) are discussed. Models of seizures in immature animals should be used for testing of potential antiepileptic drugs., P. Mareš., and Obsahuje seznam literaury
The incidence of coated vesicles under sarcolemmal surfaces of equatorial, juxtaequatorial and polar regions in developing and adult spindles of the rat soleus muscle was examined by quantitative morphometry of transverse ultrathin sections. Coated vesicles were more numerous: 1) under primary sensory endings than under other types of neuromuscular contacts; 2) under the appositional sarcolemma between neighbouring intrafusal fibres than under free surfaces of the sarcolemma; and 3) in developing than in mature spindles. Factors such as location and age of the animal often interacted to produce an additive effect on the incidence of coated vesicles. Although there was a high incidence of coated vesicles at the postsynaptic surface under sensory terminals of bag2 fibres in 18 and 19 day gestational embryonic rats, it peaked in 4 day postnatal animals. The high incidence of coated vesicles at sensory endings supports the view that coated vesicles mediate neurotrophic interactions between afferents and intrafusal Fibres during the critical late gestation and early postnatal time period, as sensory axons first contact their target fibres and exert a maximal directing influence on the differentiation of intrafusal fibre types. In addition, the preferential localization of coated vesicles under appositional rather than free surfaces of developing intrafusal fibres in 0-4 day rats suggests that they play a role in the transport of active substances among intrafusal fibres exhibiting different stages of maturity.
Neurogenic pulmonary edema (NPE), which is induced by acute spinal cord compression (SCC) unde r the mild (1.5 %) isoflurane anesthesia, is highly dependent on baroreflex-mediated bradycardia because a deeper (3 %) isoflurane anesthesia or atropine pretreatment comple tely abolished bradycardia occurrence and NPE development in rats subjected to SCC. The aim of the present study was to evaluate whether hypertension- associated impairment of baroreflex sensitivity might exert some protection against NPE developmen t in hypertensive animals. We therefore studied SCC-induced NPE development in two forms of experimental hypertension - spontaneously hypertensive rats (SHR) and salt hypertensive Dahl rats, which were reported to have reduced baroreflex sensitivity. SCC elicited NPE in both hypertensive models irrespective of their baroreflex sensitivity. It is evident that a moderate impairment of baroreflex sensitivity, which was demonstrated in salt hypertensive Dahl rats, does not exert sufficient protective effects against NPE development., J. Šedý, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
Aim of the study was to test the effect of nicotine (NIC) and kainic acid (KA) co-treatment in immature rats. Male Wistar albino rats (two different age groups) were chosen for the study. Experiments started on postnatal day (PD) 8 or 21 and animals were treated twice a day for three days with nicotine, fourth day KA was administered. Animals at PD12 (PD25 respectively) were examined electrophysiologically for cortical epileptic afterdischarges (ADs). First cortical ADs in PD12 animals were longer, when compared to PD25 rats (group treated with both substances). Nor NIC or KA treatment affected the length of discharges in PD12 rats. Older experimental group exhibited the shortening of the first ADs (group treated with NIC and KA, compared with groups exposed to single treatment). Few changes were found in KA treated group – 2nd and 4th ADs were shorter when compared with first ADs. These results demonstrate that NIC treatment played minor role in seizure susceptibility of PD12 rats, sensitivity to NIC differs during ontogenesis and subconvulsive dose of KA influenced the length of discharges only in PD25 animals., V. Riljak ... [et al.]., and Obsahuje seznam literatury
a1_The purpose of the present study was to compare the ontogenetic development of the activity of myocardial energy-supplying enzymes in two mammalian species, differing significantly in their level of maturation at birth. The animals were investigated during the late prenatal period and 2, 7, 14, 21, 25, 30, 63, 120 and 730 days after birth in the rat and 2, 21, 84 and 175 days in the guinea-pig. The following enzymes were assayed in the right and left ventricular myocardium: lactate dehydrogenase (LDH, lactate uptake and/or formation), triose phosphate dehydrogenase (TPDH, carbohydrate metabolism), glycerol phosphate dehydrogenase (GPDH, glycerol-P shuttle)), hexokinase (HK, glucose phosphorylation), malate dehydrogenase (MDH, tricarboxylic cycle), citrate synthase (CS, tricarboxylic cycle) and hydroxyacyl-CoA dehydrogenase (HOADH, fatty acid breakdown). The rat heart, highly immature at birth, exhibits three different developmental patterns of energy-supplying enzymes, identical in both ventricles: (i) two mitochondrial enzymes of aerobic metabolism (CS, HOADH) and GPDH have a relatively low activity at the end of prenatal life; thereafter their activity steadily increases, approaching the adult levels between the 3rd and 4th postnatal weeks. A significant decrease was observed between the 4th and 24th months. (ii) MDH and LDH: prenatal values were significantly higher as compared with the 2nd postnatal day; after this period the activities increased up to adulthood (4 months) and decreased during senescence. (iii) The activities of HK and TPDH are characterized by only moderate changes during development. HK differs from all other enzymes by the highest prenatal values, which exceed even adult values. In contradiction to the rat heart, the developmental differences in more mature guinea-pig heart were significantly less pronounced., a2_The only ontogenetic differences observed were the lower activities of enzymes connected with aerobic metabolism at the end of the prenatal period. Our results point to possible differences in the development of adaptive metabolic pathways in animals with different levels of maturation at birth., A. Bass, M. Stejskalová, A. Stieglerová, B. Ošťádal, M. Šamánek., and Obsahuje bibliografii