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We analyzed the role of interleukin 6 (IL-6) in modulation of the pattern of mice spontaneous activity. Wild type (WT) and IL-6 deficient mice of both sexes, young and aging, were housed individually and various types of their activity were recorded and analyzed with the Phenorack system in their home cages during 72 hours-long sessions. All investigated groups of mice were active mainly during the dark phase of the 24-hours cycle. Generally, the IL-6 deficient animals were more active than their WT controls and females of both genotypes more active than males. Aging mice were less active than the sex and genotype-matched young animals. The independent variables (age, sex and genotype) strongly interacted, which suggests that the modulatory influence of IL-6 on mice behavior may be different in males and females and that it changes during aging. We conclude that under normal physiological conditions signaling of IL-6 via its receptor participates in modulation of the basic pattern of activity. This modulation differs in males and females and changes with aging.
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The neuropeptide angiotensin II (Ang II) has been recently found to be involved in cognitive processes. Both AT1 and AT2 angiotensin receptors seem to mediate this action. However, unspecific behavioural effects of the peptide, particularly motor and emotional, appear to influence the interpretation of cognition-oriented tests and contribute to considerable differences in opinions of various authors on the subject. In this study, aimed specifically at the assessment of these effects, we found small and insignificant changes in motor performance measured in open field after intracebroventricular injections of Ang II and its receptor subtype-specific antagonists; losartan (AT1) and PD 123319 (AT2). However, Ang II was found to increase substantially anxiety measured in elevated 'plus' maze and impair motor coordination measured in 'chimney test'. Interestingly, both antagonists abolished Ang II generated anxiety and only losartan counteracted impaired motor coordination caused by the peptide. The AT2 receptor antagonist PD 123319 impairing motor coordination on its own, nonetheless partly diminished that caused by Ang II. Therefore it appears safe to conclude that mood but not motor effects of AT1 and AT2 receptor affecting drugs may significantly bias interpretation of the cognition - oriented tests on these drugs.
IL-6 is a biologically active substance and is thought to contribute to the development of obesity. Recent findings suggest that susceptibility to intracellular lipid accumulation is to a large extent determined by changes in the expression of fatty acid transporters such as FAT/CD36, FABPpm and FATP-1. The aim of the present study was to determine the effect of IL-6 deficiency on the expression of fatty acid transporters, as well as, assess the concomitant changes in intracellular lipids. We found that Il-6 deficiency upregulated the myocardial expression of FAT/CD36 (+40%) and did not significantly affect the content of FABPpm and FATP-1 (+15% and +5% respectively). Although no change in the intramyocardial total lipid content was noted, there was a significant increase in the intracellular content of both free fatty acid (FFA), diacylglicerol (DG) and ceramide fractions (+45%, +37% and +48%, respectively) in hearts from IL-6 -/- mice. A trend for IL-6 deficiency to increase in saturated FA species in these fractions was also observed (+8%, +12% and +10%, respectively). In contrast, IL-6 deficiency has no effect on the content of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) species in each intramyocardial lipid fractions examinated. These findings suggest that IL-6 deficiency results in 1) upregulation of myocardial content of FAT/CD36, 2) the increase in the content of biologically active lipid pools (FFA, DG and ceramide). This lipid accumulation with concomitant trend for increase in the saturation status of these lipid fractions may, at least in part, provide a factor related to the development of intramyocardial lipotoxicity, observed in obese individuals.
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