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We assessed the effect of intake of easily digested carbohydrates for 133 days on quantitative parameters of neuromotorics and cognitive function in Wistar rats and C57Bl/6J mice. Neuromotorics (muscle tone) was assessed in rats and mice by the forelimb muscle force (grip strength) over 4 months. Anxiety was assessed in the elevated plus-maze test and cognitive function (short-term and long-term memory) was evaluated by conditioned passive avoidance response (CPAR) test over 3 months. The mice, in contrast to rats, receiving the diet with easily digested sugars demonstrated suppression of neuromotorics. Anxiety increased with age in female mice, but not in rats, irrespective of the diet. Cognitive function in rats receiving experimental rations did not change significantly in comparison with the control. In mice, consumption of equimolar mixture of fructose and glucose impared short-term, but not long-term memory, in comparison with the group receiving glucose alone. We revealed a small (by 14-17%), but statistically significant increase in the brain weight in mice receiving fructose and sucrose. The study demonstrates sufficient interspecies differences in the influence of carbohydrate rations on neuromotorics and behavioral responses in the in vivo metabolic syndrome model.

BACKGROUND: The peptidic hormone leptin (Lep) occupies a central place in the control of energy homeostasis and body weight in mammals. A convenient model for studying the role of impaired Lep reception is the Zucker-LEPRfa rats, which carry a mutation in the homozygote of the LEPR gene. Quercetin (Q; 3.3 ‘, 4’, 5.7-pentahydroxyflavone) is currently being considered as one of the promising biologically active substances, which allows to correct metabolic disorders in obesity and metabolic syndrome. AIM: to study changes in the expression of genes in liver tissue of rats with impaired receptivity of Lep under the influence of high-fat and high-carbohydrate diet (HFCR) or/and Q supplementation. MATERIAL AND METHODS: 4 groups of six male Zucker-LEPRfa male rats were used in experiment. Within 61 days the animals of the 1st group (control) received a balanced semi-synthetic diet, the second group received the same diet with the addition of quercetin in a dose of 50 mg/kg of body weight, the third group — the HFCR (30% fat by dry weight and 20% fructose instead of water), the 4th group is the same diet and supplement of quercetin. Full transcriptional profiling of liver tissue was performed on microchips from the Gene Expression Hybridization Kit (Agilent Technologies), a real-time polymerase chain reaction combined with reverse transcription (RT-PCR) was performed for liver transcripts of Crot, FTO, NpY, Prdx1, Prom1, Ugt2b37 and GAPDH genes contained in liver tissue. RESULTS: It was shown that feeding of Zucker-LEPRfa rats with Q and/or HFCR led to significant changes in the level of transcription of 1604 genes in liver tissue, from which the effect of quercetin proper was manifested for 1396 genes. Changes were more pronounced in the transcriptome of liver tissue caused by HFCR, than caused by the addition of Q against the background of a standard diet. Q influenced the expression of genes responsible for xenobiotic detoxification processes (UGT2b37), redox homeostasis (Prdx1), beta-oxidation of fatty acids (Crot), and central mechanisms affecting hunger and satiety (NpY), and potentiated, or abolished the effects of HFCR against a number of other functionally important genes. Bioinformatic analysis revealed the influence of HFCR and/or Q on 23 metabolic pathways (KEGGS), of which 7 (the metabolism of steroids, arachidonic and linoleic acids, retinoids, drugs and xenobiotics (due to cytochrome P-450), bile secretion) were affected in all experimental groups. CONCLUSIONS: Changes in the transcriptome of the liver of Zucker-LEPRfa rats, caused by consumption of HFCR and/or Q, were consistent with experimental data on changes in short-term memory, anxiety and mineral metabolism in these animals.

The methods of laser confocal microscopy were employed to study the changes in rat target organs (iliac mucosa and liver) provoked by peroral administration of dispersion of nanosized (31 nm) multimolecular fullerene C60 particles in doses of 0.1, 1.0, and 10 mg/kg body weight over 92 days. The micropreparations were selectively stained with fluorescent dyes to mark the cell nuclei (DAPI), actin microfilaments (fluorescently labeled phalloidin), and the membrane proteins CD106, CD31, and claudins in tight junctions (fluorescently labeled monoclonal antibodies). In rats treated with fullerene in the examined doses, the iliac mucosa demonstrated normal morphology of the villi. There were no signs of inflammation and no alterations in the actin fi laments of cytoskeleton and in enterocytic tight junctions. The count of CD106(+) and CD31(+) cells did not change. The highest examined doses of fullerene (1 and 10 mg/kg body weight) increased population and modified distribution of hepatic CD106(+) cells. They also resulted in accumulation of cytoplasmic granules presumably identified as Kupffer macrophages without any signs of visible inflammation or necrotic areas. This phenomenon can reflect the early stages of toxic reaction being a sensitive bioindicator of the damage produced by administered fullerene C60 in the hepatic tissue.

The effect of daily intragastric administration of an aqueous dispersion of silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body weight for 28 days) to rats on the proteomic profile of liver microsomes has been investigated by 2D-electrophoresis followed by subsequent mass spectrometry identification. The liver microsomal fraction was isolated by differential centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel electrophoresis. Identification of protein spots was carried out using MALDI-TOF mass spectrometric analysis. The mass spectrometry analysis revealed the protein GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of heat shock proteins. This protein present in animals of the control group was not detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10 mg/kg body weight/day). This protein predominantly localized in the liver cell endoplasmic reticulum and plasma membrane has the chaperone biological activity. Possible mechanisms of the effects of engineered nanoparticles on biosynthetic processes in the body are discussed.

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