The first experimental model of atherosclerosis (in rabbits) is more than hundred years old. Several animal species have bee n used to produce hyperlipoproteine mia and possible atherosclerosis. The gene manipulation produced the most used models recently. This review acknowledges the extensive study of atherosclerotic changes in experimental models of hyperlipoprotein emia and at herosclerosis to come to light thus far and the purpose here is not only to summariz e the published data but also to try to add some details of our experience in using these models. In addition to rabbit (the old but also improved model by reno-vascular hy pertension) dog, birds, pig, hamster, mice, rat and non-human primate’s animal models are described. The gene manipulation produced the most used models two decades ago. Germline genetically engineered (without apoE or LDL receptor genes) animals have beco me the most used models producing atherosclerotic changes in the aorta. Recent new models also producing atherosclerotic changes but without germline genetic manipulation are also described., R. Poledne, L. Jurčíková-Novotná., and Obsahuje bibliografii
a1_In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic -ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG -saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituat ing to the environment in the repeated spatial environment, but rats with immuno - or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno - or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS - lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory;, a2_(iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field - the memory exhibited by decrements in exploration of repeated object presentations is affected by either electr olytic or ibotenic lesions, but not saporin., M. G. Dashniani, M. A. Burjanadze, T. L. Naneishvili, N. C. Chkhikvishvili, G. V. Beselia, L. B. Kruashvili, N. O. Pochkhidze, M. R. Chighladze., and Obsahuje bibliografii
It is known that psychostimulants including methamphetamine (MA) have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed on evaluation of cognitive changes following scheduled prenatal MA exposure in combination with long-term exposure in adulthood of male rats. Two periods of gestation were targeted: 1st half - the embryonic day (ED) 1-11 and 2nd half - ED 12-22. Rat mothers received subcutaneously a daily injection of MA (5 mg/kg) or saline (SAL, 1 ml/kg) throughout scheduled periods. Male offspring were tested for cognitive changes in the Morris Water Maze (MWM) in adulthood. Each day of the experiment animals received an injection of MA (1 mg/kg) or SAL (1 ml/kg) during 12 days. Our results demonstrated that in the group of animals exposed to the drug during ED 1-11, neither prenatal MA exposure, nor adult MA treatment changed the performance in the MWM test. Only the velocity was increased in group with long-term MA treatment (SAL/MA and MA/MA). In the group of animals exposed to the drug during ED 12-22, rats exposed to MA prenatally and also in adulthood (MA/MA) swam faster but learned the position of the platform slower in the Place Navigation Test than animals exposed to SAL in adulthood (MA/SAL). In the Probe Test, MA/SAL had decreased velocity and swam shorter distance than MA/MA or SAL/SAL rats suggesting increased floating of these animals. In the Memory Retention Test, SAL/MA rats swam shorter distance than SAL/SAL or MA/MA animals suggesting changes in used strategies in memory recall. As conclusion, our results suggest differences in the effect of combination of prenatal and adult exposure to MA. These effects further depend on the stage of CNS development and schedule of MA exposure affecting intrauterine development in male rats., I. Hrebíčková, M. Malinová-Ševčíková, E. Macúchová, K. Nohejlová, R. Šlamberová., and Obsahuje bibliografii
Aquaporins (AQPs) are water channel proteins responsible for water homeostasis and important for proper functioning of all body systems, including reproductive structures. This study was designed to determine their localization and quantitative changes in the pig ovary during different stages of the estrous cycle and early pregnancy. The expression of AQP 1, 5 and 9 proteins was determined by immunocytochemistry and Western blot analyses. AQP1 was found in the plasma membranes of capillary endothelium, AQP5 - in the plasma membranes of granulosa cells of developing follicles and flattened follicle cells of the primordial follicles, and AQP9 - in granulosa cells of the developing follicles. In the cyclic pigs, the expression of AQP1 and 5 proteins was the highest on Days 18-20, but did not change significantly between Days 2-4, 10-12 and 14-16 of the cycle. In pregnant pigs (Days 14-16 and 30-32), the expression of AQP1 and 5 did not change and was similar to that observed during Days 10-12 and 14-16. In turn, AQP9 expression did not change between all studied periods. In conclusion, studied AQP are localized in different cells populations, the endothelial and granulosa cells, and AQP1 and 5 seem to be crucial for follicular development in pigs., A. Skowronska, P. Mlotkowska, M. Eliszewski, S. Nielsen, M. T. Skowronski., and Obsahuje bibliografii
Hypoxia-inducible factor-1α (HIF-1α) transcriptionally regulates expression of several target genes in protecting tissues against hypoxia. With hypoxic stress, vascular endothelial growth factor (VEGF) is a signal protein produced by cells and further contributes to improvement of vascular functions and restoring the oxygen supply to tissues. In this current study, we first hypothesized that the protein levels of HIF-1α and VEGF are reduced in skeletal muscles of plateau animals [China Qinghai- Tibetan plateau pikas (ochotona curzoniae)] in response to hypoxia as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. We further hypothesized that HIF-1α plays a role in regulating expression of VEGF in skeletal muscle. Note that HIF-1α and VEGF were determined by using two-site immunoenzymatic assay (ELISA) methods. Our results demonstrated that hypoxic stress induced by exposure of lower O2 (6 h) significantly increased the levels of HIF-1α and VEGF in the oxidative and glycolytic muscles of SD rats and pikas (P<0.05 vs. normoxic conditions). Notably, the increases in HIF-1α and VEGF were significantly less in pikas (P<0.05, vs. SD controls) than in SD rats. In addition, a linear relationship was observed between amplified HIF-1α and VEGF in oxidative muscle (r=0.76 and P<0.01) and glycolytic muscle (r=0.72 and P<0.01) and inhibiting HIF-1α significantly decreased expression of VEGF induced by hypoxic stress in skeletal muscles (P<0.05). Overall, our findings suggest that (1) responsiveness of HIF-1α and VEGF in skeletal muscles to hypoxic stress is blunted in plateau animals, and (2) HIF-1α has a regulatory effect on VEGF under hypoxic environment., H.-C. Xie, J.-P. He, J.-F. Zhu, J.-G. Li., and Obsahuje bibliografii
Serotonin receptors have been found in several reproductive organs as well as in the central nervous system. Serotonin-binding sites have been demonstrated in duck ovarian follicles and the testis, hamster ovaries, human granulosa cells and mouse placenta. Local production of serotonin by the rat ovary, oviduct, uterus and testis has also been reported. We analyzed the expression of three types of serotonin receptors: 5-HT1B, 5-HT2C and 5-HT1D by reverse transcription-polymerase chain reaction in mouse unfertilized oocytes and preimplantation embryos from zygotes to the blastocyst stage in vivo. Transcripts for 5-HT1B and 5-HT2C serotonin receptors were detected neither in unfertilized oocytes nor at any stages of in vivo developing preimplantation embryos. Serotonin 5-HT1D receptor mRNA was present in unfertilized oocytes, zygotes, 2-cell embryos, compacted morulae and in vivo produced expanded blatocysts. The expression of the mRNA 5-HT1D serotonin receptor was also detected in blastocysts cultured in vitro. When added to the culture medium, specific serotonin 5-HT1D agonist sumatriptan (1 μM) significantly inhibited the development of mouse embryos cultured in vitro. Demonstration of the expression of 5-HT1D serotonin receptor in mouse oocytes and preimplantation embryos supports the idea of a functional serotonin (5-HT1D) receptor in early mammalian development., J. Veselá, P. Rehák, J. Mihalik, S. Czikková, J. Pokorný, J. Koppel., and Obsahuje bibliografii
Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. As obesity and diabetes are common in several ciliopathies, we aimed to analyze changes of gene expression within Nme7 interactome in genetically designed rat models of metabolic syndrome. We assessed the liver transcriptome by Affymetrix microarrays in adult males of 14 PXO recombinant inbred rat strains and their two progenitor strains, SHR-Lx and BXH2. In the strains with the lowest expression of Nme7, we have identified significant enrichment of transcripts belonging to Nme7 interactome. In the subsequent network analysis, we have identified three major upstream regulators - Hnf4a , Ppara and Nr1h4 and liver steatosis (p=0.0001) and liver necrosis/cell death (apoptosis of liver cells, p=0.0003) among the most enriched Tox categories. The mechanistic network reaching the top score showed substantial overlap with Assembly of non-motile cilium and Glucose metabolism disorder gene lists. In summary, we show in a genetic model of metabolic syndrome that rat strains with the lowest expression of Nme7 present gene expression shifts of Nme7 interactome that are perturbing networks relevant for carbohydrate and lipid metabolism as well as ciliogenesis., L. Šedová, E. Školníková, M. Hodúlová, J. Včelák, O. Šeda, B. Bendlová., and Obsahuje bibliografii
The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction α (α = ECS volume/ total tissue volume), 2. tortuosity λ (λ2 = free /apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k’. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter „spillover“ and synaptic cross-talk as well as cell migration, drug delivery and treatment., L. Vargová, E. Syková., and Obsahuje bibliografii a bibliiografické odkazy
Apolipoprotein E (apoE) is a polymorphic protein which occurs in three common isoforms and more than 25 rare variants. Some of the rare apoE variants have been implicated in a dominant mode of inheritance of familial dysbetalipoproteinemia (FD). We have identified three unrelated apoE 2*(Arg136®Cys) carriers with FD. This finding supports the notion that although apoE 2*(Arg136®Cys) mutation is perhaps not sufficient to cause FD itself, the presence of other genetic and/or environmental factors can lead to the phenotypic expression of the disease in the carriers., M. Vrablík, A. Hořínek, R. Češka, T. Štulc, T. Kvasnička., and Obsahuje bibliografii
Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a de crease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treat ment and prevent cardiov ascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is on e of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the futur e and enable even more accessible and accurate genetic diagnostics., M. Vrablík, M. Vaclová, L. Tichý, V. Soška, V. Bláha, L. Fajkusová, R. Češka, M. Šatný, T. Freiberger., and Obsahuje bibliografii