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Perseveration, defined as resistance to change in routine and repetitive behaviors, is one of the core symptoms of Autism Spectrum Disorders. It was proposed that an inability to break habits, experienced by autistic people, corresponds, in animal models, to impaired performance in the learning tasks that assess ability to change a response strategy to obtain reinforcement. However, the results of conventional behavioral tests can be confounded by anxiety related to handling and social isolation. In order to avoid such effects and to analyze phenotypes of subjects in an efficient manner, we developed a battery of automated tests aimed at appraising behavioral flexibility in mice. The tests were performed in the IntelliCage (IC), a computer-controlled system, which can be used for long-term monitoring of group-housed animals. These tests allow for measuring of exploration patterns, pace and progress of appetitive and reversal learning. To standardize and evaluate the relevant IC tests, we compared valproate treated and control animals from two inbred strains of mice, C57BL/6 and BALB/c. We show that tested mice differ significantly in most of the examined parameters. The obtained results are highly replicable between tested cohorts of subjects, thereby allowing us to infer, that the reported battery of automated behavioral and cognitive tests is a valuable tool in verifying suitability of mouse models of ASD symptoms.
Objectives: Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in the pathogenesis of this disease is not clear. Assessment of retinol binding protein (RBP-4) seems to be promising because data from animal and human studies suggest its role in the patomechanism of insulin resistance. Therefore, the aim of the study was to evaluate the serum levels of RBP-4 in children with NAFLD. Methods: Fasting serum level of RBP-4 was determined in 42 obese children with suspected liver disease and 20 lean controls. The degree of liver steatosis was graded in ultrasound according to Saverymuttu. The intrahepatic lipid content was assessed noninvasively in a semiquantitative fashion using 1HMR spectroscopy (1.5-T scanner with PRESS sequence). Results: Fatty liver was confirmed in 30 children by ultrasonography (16 of them had also increased alanine transaminase (ALT) activity). Serum concentrations of RBP-4 were significantly higher in obese children with NAFLD compared to controls. Significant correlations were found between RBP-4 level and ultrasonographic grade of liver steatosis, intrahepatic lipid content (1HMRS) and triglycerides level, while the serum level of RBP-4 was not significantly higher in children with advanced liver steatosis (grade 2-3, n = 11) compared to patients with mild steatosis (grade 1, n = 19). The ability of RBP-4 to differentiate children with advanced liver steatosis from those with mild steatosis was not significant. Conclusion: RBP-4 can be considered as a convenient serum marker of intrahepatic lipid content in obese children.
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