Effects of anthocyanin-rich grain diet on growth and metastasis of Lewis lung carcinoma in mice

Poster (download) Michael V. Tenditnik1, Maria A. Tikhonova2, Ekaterina A. Litvinova3, Nelly A. Popova4, Tamara G. Amstislavskaya5, Elena K. Khlestkina61Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, m.v.tenditnik@physiol.ru2Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, tikhonovama@physiol.ru3Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, litvinovaea@physiol.ru4Federal Research Center “Institute of Cytology and Genetics” Novosibirsk, Russia, nelly@bionet.nsc.ru5Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, Amstislavskaya@yandex.ru6N.I. Vavilov All-Russian Research Institute of Plant Genetic Resources St. Petersburg, Russia, Federal Research Center “Institute of Cytology and Genetics” Novosibirsk, Russia, khlest@bionet.nsc.ru Abstract Currently functional nutrition has developed intensively. Functional foods are a valuable addition to existing dietary therapy. Such products are enriched with biologically active substances. Anthocyanins attract particular attention due to multiple beneficial properties including antitumor activity. Here we used two wheat near-isogenic lines created at the Institute of Cytology and Genetics SB RAS [1] that have almost similar genomes with the exception of a small part of chromosome 2A, which contains the Pp3/TaMyc1 gene regulating anthocyanin biosynthesis, to assess the effect of an anthocyanin-rich grain diet on the development and metastasis of the Lewis lung carcinoma (LLC), as well as the accompanying immune response in C57BL/6 mice. Mice were kept at a grain or standard diet for four month prior tumor transplantation. A decrease in the number of metastases in the lungs and the size of the tumor in the groups at a grain diet, regardless of the content of anthocyanins, was revealed. However, the highest percentage of animals without metastases was observed at an anthocyanin-rich grain diet. The LLC transplantation caused a significant increase in plasma levels of pro-inflammatory cytokines (IL-6 and LIF) in mice at a standard diet, but not in animals at grain diets. Thus, the anthocyanin-rich diet helps to reduce the severity of the tumor process. The antitumor effects of grain diets are probably mediated by modulation of signaling pathways associated with IL-6 cytokines. Acknowledgment The study was supported by Russian Science Foundation (grant No. 16-14-00086). References I. Gordeeva, O. Y. Shoeva, and E. K.Khlestkina, “Marker-assisted development of bread wheat near-isogenic lines carrying various combinations of purple pericarp (Pp) alleles,” Euphytica, vol. 203, pp. 469-476, 2015.

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Interplay between 5-HT and BDNF system in recombinant mouse strain upon chronic fluoxetine administration

Poster (download) Rodnyy A.Ya.1, Kondaurova E.M2, Antonov Y.V.3, Ilchibaeva T.V.4, Tsybko A.S.5, Naumenko V.S.61Institute of Cytology and Genetics Novosibirsk, Russia, aleksandr1994rodny@gmail.com2Institute of Cytology and Genetics Novosibirsk, Russia, kond_em@bionet.nsc.ru3Institute of Cytology and Genetics Novosibirsk, Russia, yegor@bionet.nsc.ru4Institute of Cytology and Genetics Novosibirsk, Russia, rbicehok@mail.ru5Institute of Cytology and Genetics Novosibirsk, Russia, antontsybko@bionet.nsc.ru6Institute of Cytology and Genetics Novosibirsk, Russia, naumenko2002@bionet.nsc.ru BDNF plays a key role in the development, differentiation, synaptogenesis and survival of brain neurons and in the processes of their adaptation to external impacts. Serotonergic (5-HT) system is another basic player in brain development and neuroplasticity. The study presents a comparative analysis of chronic fluoxetine treatment in recombinant mice differing in distal chromosome 13 fragment containing Htr1A gene of CBA mice strain on C57Bl6 genetic background. The problem here to be studied is mechanism of BDNF and 5-HT systems` interactions in antidepressant insensitivity. We measured mRNA and protein levels of BDNF, p75NTR, TrkB, 5-HT1A and 5-HT7 receptors, levels of 5-HT and its primary metabolite 5-Hydroxyindoleacetic acid (5-HIAA) in the brain structures that could have play primary role in mechanism of depression – frontal cortex and hippocampus. At the heart of the discussion are the different changes in BDNF system as well as in 5-HT system which allows us to conclude that the chronic fluoxetine injection increased depressive-like behavior in recombinant mice carrying distal chromosome 13 fragment containing Htr1A gene of CBA mice.

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Possibilities of enhancing the neuroprotective effect of autophagy activation in the brain by stimulation of an mTOR-independent pathway of its regulation in a transgenic mouse model of Parkinson’s disease

Akopyan A.A.1, Pupyshev A. B2, Tikhonova M.A.31Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, annaaleksanovna@mail.ru2Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, apupyshev@mail.ru3Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, mar-a-tikh@mail.ru Autophagy induction promotes cell survival that is especially important for neurons which have a limited proliferative resource. Autophagy is regulated by the classical mTOR-dependent mechanism activated by rapamycin, and also via mTOR-independent pathways triggered by trehalose, lithium, metformin, etc. The neuroprotective effect was shown upon combined activation of these pathways in vitro. However, the possibilities of enhancing the therapeutic effect of autophagy activation in vivo remain unclear. Transgenic mice of B6.Cg-Tg (Prnp-SNCA*A53T)23Mkle/J strain with overexpression of alpha-synuclein were used as a model of Parkinson’s disease (PD) in the study. In the striatum and substantia nigra, which are mainly affected in PD, trehalose caused an increase in autophagy, as measured by the expression of the autophagy marker LC3-II. Trehalose in combination with rapamycin increased LC3-II expression by two to three times in comparison with the action of rapamycin alone. In the frontal cortex no changes in LC3-II expression were observed neither under the action of trehalose nor with the combined treatment with trehalose and rapamycin. The most pronounced neuroprotective effect was observed upon the combined use of rapamycin and trehalose by the tyrosine hydroxylase expression in the nigrostriatal system marking the restoration of dopaminergic neurons. In the Rotarod test, the mice were tested for motor function. Animals treated with rapamycin, trehalose, or their combination stayed much longer on a rotating drum, compared to controls. Autophagy contribution to the therapeutic effects was confirmed by administration of autophagy inhibitor 3-methyladenine, which completely blocks the neuroprotective effects of the drugs. Acknowledgments This work was supported  by a grant No. 16-04-01423 from the Russian Foundation for Basic Research.

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The impact of early-life stress on the expression of genes associated with the formation of the myelin sheath of neurons in the prefrontal cortex of 15-day-old male mice

Poster (download) Anastasia S. Shulyupova1, Arina A. Smelova2, Vasiliy V. Reshetnikov3, Natalya P. Bondar41Laboratory of Gene Expression Regulation Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, IРЎ&G SB RAS, shulyupova@bionet.nsc.ru2Epigenetics laboratory National Research Novosibirsk State University, NSU, smelovarina@gmail.com3Laboratory of Gene Expression Regulation Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, IРЎ&G SB RAS, vasiliyreshetnikov@bionet.nsc.ru4Laboratory of Gene Expression Regulation Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, IРЎ&G SB RAS, nbondar@bionet.nsc.ru The early postnatal period is critical for the development of the central nervous system and can predetermine subsequent behavioral patterns, so stress at this age can lead to long-term consequences in adulthood. In our work, we investigated effects early life stress on myelination. We assessed the expression of the genes associated with the myelin sneath (myelin basic protein – Mbp, myelin-associated oligodendrocyte basic protein – Mobp, proteolipid protein 1 – Plp1, proteolipid in compact myelin – Mal, myelin oligodendrocyte glycoprotein – Mog, choline-specific glycerophosphodiester-phosphodiesterase – Enpp6, UDP-glucuronosyltransferase – Ugt8a) in frontal cortex of mice. The greatest difference in the level of expression was found between groups with a maternal deprivation and a maternal separation from mothers: significant changes were shown for the Enpp6, Mal, Ugt8a genes and one of the Mobp gene transcripts. This may indicate a different extent of exposure to stressors. We can conclude that the stress in the early postnatal period affects the myelination process and can lead to impaired transmission of nerve impulses.

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Effect of overexpression of the 5-HT7 receptor gene on behavior and brain serotonin system in ASC mice with predisposition to depressive-like behavior

Baraboshkina I.A.1, Bazovkina D.V.2, Ilchibaeva T.V.3, Antonov E.V.4, Kulikova E.A.5, Naumenko V.S.61ICG SB RAS, irina.10.24@yandex.ru2ICG SB RAS, daryabazovkina@gmail.com3ICG SB RAS, rbicehok@mail.ru4ICG SB RAS, a.yegor.v@gmail.com5ICG SB RAS, kulikova.elisa@gmail.com6ICG SB RAS, naumenko2002@gmail.com Abstract The serotonin (5-HT) system of the brain plays an important role in controlling various behaviors due to the wide variety of serotonin receptors. The 5-HT7 receptor is of great interest because it is involved in the pathogenesis of depressive disorders. Mice of ASC (Antidepressant Sensitive Catalepsy) line with genetic predisposition to depressive-like behavior were obtained in the Laboratory of Behavioral Neurogenomics of ICG SB RAS (Novosibirsk). In this work, the effect of adenoassociated virus (AAV)-mediated overexpression of the 5-HT7 receptor gene in the midbrain on the behavior and brain serotonin system in ASC mice was comprehensively studied. The ASC mice with overexpression of 5-HT7 receptor gene showed the decrease in depressive-like behavior in the forced swim test compared to control group. The introduction of a vector construct with the 5-HT7 receptor gene affected the expression of the gene encoding the 5-HT7 receptor itself, only in the midbrain. The overexpression of 5-HT7 receptor gene in midbrain led to an increase in the serotonin metabolism index in the cortex, hippocampus, and midbrain of mice, without affecting serotonin levels. The results indicate the effect of overexpression of the 5-HT7 receptor gene on the behavior and serotonin system of the brain in ASC mice with a genetic predisposition to depressive-like behavior.

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Compulsive-like behaviors in DISC1-mice

Poster (download) Nadezhda Chizhova1, Kristina Smirnova21ICG SB RAS, chnadezhda1995@gmail.com2NSU, PhBMRI, vedelina@mail.ru The DISC1 gene is associated with the development of mental disorders in humans. Currently a number of genetic models of psychopathologies withВ  mutations in the gene have been created, including genetic lines of mice with point mutations DISC1-Q31L-/- (model of depression) and DISC1-L100P-/- (model of schizophrenia), which are available at the unique scientific installation “Biological collection – genetic biomodels of neuropsychiatric diseases” (State Scientific-Research Institute of Physiology and Basic Medicine, Novosibirsk). In additional mice DISC1-Q31L-/- showed compulsive-like behavior, and in this connection was proposed to study this type of behavior in heterozygotes and diheterozygotes for these mutations. The work performed allows us to conclude that the presence of only one mutant allele (both DISC1-Q31L and DISC1-L100P) is not sufficient for the expression of compulsive-like behavior in mice. However, mice that combine both mutations are predisposed to this behavior and exhibit it depending on their sex and mother’s genotype: this behaviour characterise males whose mothers were homozygous for DISC1-Q31L mutation, and females whose mothers were homozygous for DISC1-L100P mutation. The conclusion about the influence of homozygosity and, accordingly, the behavior of mothers on the compulsive-like behavior of females and males can be verified in further experiments.

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