The role of the striatal adenylyl cyclase (AC) and cholinergic systems in the learning and expression of new forepaw movements (reaching with prolonged pushing on a fixed piston) was studied in male Wistar rats. Motor learning processes, prenatal hypoxia, and cholinergic drugs changed the properties of the AC system in the striatum. After learning, the striatal basal AC activity was decreased compared to untrained control rats. In addition, the AC activity was more decreased in animals with a good ability to learn compared to poor learners (up to 31 % and 51 %, correspondingly; p<0.01). Rats subjected to prenatal hypoxia (13-14th days of embryogenesis) had a lower ability to learn the new movements requiring tactile control and the striatal AC activity in these rats was 1.8 times higher (p<0.001) than controls. In vitro application of the cholinergic agonist carbachol (CARB) 10-5 M (corresponding to ~ 0.3 µg), as well as the antagonist scopolomine (SCOP) 10-5 M (~ 0.3 µg) decreased AC activity in the synaptosomal fraction of the striatum. In vivo injections of CARB (0.3-3 µg/1µl) or SCOP (0.3-3 µg/1µl) into the ventral striatum (nucleus accumbens) modified the newly learned sensorimotor skill. After CARB injections the rats performed slower movements with more prolonged pushing. After SCOP the rats could not retain the learned pushing movement. These in vivo and in vitro data suggest that the cholinergic mediator system of the striatum is involved in learning sensory-controlled forepaw movements as well as the regulation of new motor skills by modulating the AC signal transduction process in the striatum. The data confirmed that modification of the striatal AC system resulted in the modulation of reaching behavior and better expression of the learned reflex., I. A. Zhuravin, N. M. Dubrovskaya, S. A. Plesneva., and Obsahuje bibliografii
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of ou r study was to confirm the association between NYD-SP18 rs6971091 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the si multaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971091 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971091 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males., J. A. Hubacek, D. Dlouha, V. Lanska, V. Adamkova., and Obsahuje bibliografii
NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are also characterized by use-independent unblock, compatible with minimal disruption of normal synaptic transmission. Thus, neurosteroids are a promising class of NMDA receptor modulators that may lead to the development of neuroprotective drugs with optimal therapeutic profiles., V. Vyklicky ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent., L. Zhang, W. Zhao, C. Zhao, H. Jin, B. Wang, B. Wang., and Seznam literatury
a1_The long-term feeding of a high-concentrate diet (the concentrate ratio is greater than 60 %) leads to mammary gland inflammatory response in ruminants and decreased quality in dairy cows and affects the robust development of the dairy industry. The main reason is closely related to elevated lipopolysaccharide (LPS) in the body. In this experiment, a bovine mammary epithelial cell line (MAC-T) was used as a model, and LPS at different concentrations (0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, 10000 ng/ml) was added to the cells. The cell survival rate, oxidative stress indicators, total lipid droplet area, triglyceride content and key genes regulating lipid metabolism were detected by 3-(4,5)-dimethylthiahiazo(-z-y1)- 3,5-di-phenytetrazoliumromide (MTT), assay kit, microscope observation and RT-PCR methods to explore the regulatory mechanism of mammary health and milk fat synthesis.The results showed that compared with those of the control group, the survival rates of cells were significantly decreased after 9 h of stimulation with 1000 ng/ml and 10000 ng/ml LPS (P<0.01).The contents of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in cells were significantly decreased (P<0.05).Compared with that of the control group, the content of malondialdehyde (MDA) in cells was significantly increased (P<0.05) after stimulation with 10000 ng/ml LPS for 9 h. After 9 h of stimulation with 100 ng/ml, 1000 ng/ml and 10000 ng/ml LPS, the total lipid drop area and triglyceride (TG) content of MAC-T cells were significantly decreased (P<0.05).The expression levels of fatty acid synthesis-related genes AcetylCoA carboxylase (ACC) and Stearoyl-CoA desaturase 1 (SCD-1) were significantly decreased after 9 h of stimulation with 100 ng/ml, 1000 ng/ml and 10000 ng/ml LPS (P<0.05), while the expression levels of Fatty Acid synthetase (FAS) were significantly decreased after stimulation with 1000 ng/ml and 1000 ng/ml LPS (P<0.05)., Lin Li, Weibin Tang, Mei Zhao, Binbin Gong, Meng Cao, Jianyuan Li., and Obsahuje bibliografii
Our study aimed to investigate subacute exposure to alcohol in relation to bone microstructure of mice. Animals from experimental (E) group drank a solution composed of 15 % ethanol and water for 14 days (one remodeling cycle), while those from control (C) group drank only water. In the compact bone of E group, decreased bone formation and increased porosity were observed which corresponds with lower levels of serum alkaline phosphatase and glutathione. Alcohol significantly increased sizes of primary osteon's vascular canals and decreased those of secondary osteons, Haversian canals. Relative bone volume, bone mineral density (BMD), relative bone volume without marrow cavity were also lower in E group. On the contrary, trabecular bone microstructure did not differ significantly between E and C groups. Liver function test showed higher levels of alanine aminotransferase, aspartate aminotransferase in alcohol-fed mice. Serum calcium, phosphate were significantly lower in E group. According to our study, only changes in compact bone microstructure of mice following one remodeling cycle were observed due to both direct and indirect effects of alcohol., A. Sarocka, V. Kovacova, R. Omelka, M. Bauerova, E. Kapusta, Z. Goc, G. Formicki, M. Martiniakova., and Obsahuje bibliografii
Agonist-induced subcellular redistribution of G-protein coupled receptors (GPCR) and of trimeric guanine-nucleotide binding regulatory proteins (G-proteins) represent mechanisms of desensitization of hormone response, which have been studied in our laboratory since 1989. This review brings a short summary of these results and also presents information about related literature data covering at least small part of research carried out in this area. We have also mentioned sodium plus potassium dependent adenosine triphosp hatase (Na, K-ATPase) and 3H-ouabain binding as useful reference standard of plasma membrane purity in the brain., Z. Drastichová, L. Bouřová, V. Lisý, L. Hejnová, V. Rudajev, J. Stöhr, D. Durchánková, P. Ostašov, J. Teisinger, T. Soukup, J. Novotný, P. Svoboda., and Obsahuje bibliografii a bibliografické odkazy
Kainic acid (KA) is a potent neurotoxic substance valuable in research of temporal lobe epilepsy. We tested how subconvulsive dose of KA influences spontaneous behavior of adult Wistar rats. Animals were treated with 5 mg/kg of KA and tested in Laboras open field test for one hour in order to evaluate various behavioral parameters. Week after the KA treatment animals were tested again in Laboras open field test. Finally, rat’s brains were sliced and stained with Fluoro-Jade B to detect possible neuronal degeneration. Treatment with KA increased the time spent by locomotion (p<0.01), exploratory rearing (p<0.05) and animals traveled longer distance (p<0.01). These parameters tended to increase thirty minutes after KA administration. Week after the treatment we did not found differences in any measured behavioral parameter. Histology in terms of Fluoro-Jade B staining did not reveal any obvious neuronal damage in hippocampus. These results demonstrate that subconvulsive KA dose changes the behavioral parameters only transiently. Clarification of timing of the KA induced changes may contribute to understand mutual relationship between non-convulsive seizures and behavioral/cognitive consequences., V. Riljak, D. Marešová, J. Pokorný, K. Jandová., and Obsahuje bibliografii
Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 ºC). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy., C. Neacsu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Cardiovascular (CV) mortality was reduced more than 50 % in the Czech population at the turn of the century, due to an improvement of major CV risk factors in the general population, interventional procedures implemented into the treatment of acute coronar y events, and new drugs (ACE inhibitors, statins etc.) for CV prevention (Czech MONICA and post-MONICA studies, 1985-2008). An insufficient level of preventive efforts is described in the Czech patients after acute coronary syndrome (Czech part of the EURO ASPIRE studies, 1995-2013). Drug underdosing and wrong patients’ compliance to life style and drug therapy recommendations represent two main reasons of this unsatisfactory situation. The residual vascular risk of patients with stable coronary heart diseas e (CHD) is still high due to a poor control of conventional risk factors on the one hand, and due to increasing weight and glucose metabolism abnormalities on the other hand. Patients with insulin resistance and glucose dis orders have more frequently non-LDL-C dyslipidemia (atherogenic dyslipidemia), hypertriglyceridemic waist and high atherogenic index of plasma (AIP>0.24), i.e. markers of residual CV risk. Among others increased dose of statins and combined lipid modifying therapy should be implemented in patients with CHD, diabetes or metabolic syndrome., H. Rosolová, B. Nussbaumerová, O. Mayer Jr., R. Cífková, J. Bruthans., and Obsahuje bibliografii