8 research outputs found

    Effect of Short Photoperiod on Behavior and Brain Plasticity in Mice Differing in Predisposition to Catalepsy: The Role of BDNF and Serotonin System

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    Seasonal affective disorder is characterized by depression during fall/winter as a result of shorter daylight. Catalepsy is a syndrome of some grave mental diseases. Both the neurotransmitter serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are involved in the pathophysiological mechanisms underlying catalepsy and depressive disorders. The aim was to compare the response of behavior and brain plasticity to photoperiod alterations in catalepsy-resistant C57BL/6J and catalepsy-prone CBA/Lac male mice. Mice of both strains were exposed for six weeks to standard-day (14 h light/10 h darkness) or short-day (4 h light/20 h darkness) conditions. Short photoperiod increased depressive-like behavior in both strains. Only treated CBA/Lac mice demonstrated increased cataleptic immobility, decreased brain 5-HT level, and the expression of Tph2 gene encoding the key enzyme for 5-HT biosynthesis. Mice of both strains maintained under short-day conditions, compared to those under standard-day conditions, showed a region-specific decrease in the brain transcription of the Htr1a, Htr4, and Htr7 genes. After a short photoperiod exposure, the mRNA levels of the BDNF-related genes were reduced in CBA/Lac mice and were increased in the C57BL/6J mice. Thus, the predisposition to catalepsy considerably influences the photoperiodic changes in neuroplasticity, wherein both C57BL/6J and CBA/Lac mice can serve as a powerful tool for investigating the link between seasons and mood

    Effect of Central Administration of Brain-Derived Neurotrophic Factor (BDNF) on Behavior and Brain Monoamine Metabolism in New Recombinant Mouse Lines Differing by 5-HT1A Receptor Functionality

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    Experiments were carried out on recombinant B6.CBA-D13Mit76C (B6-M76C) and B6.CBA-D13Mit76B (B6-M76B) mouse lines created by transferring a 102.73–118.83 Mbp fragment of chromosome 13, containing the 5-HT1A receptor gene, from CBA or C57BL/6 strains to a C57BL/6 genetic background, correspondingly. We have recently shown different levels of 5-HT1A receptor functionality in these mouse lines. The administration of BDNF (300 ng/mouse, i.c.v.) increased the levels of exploratory activity and intermale aggression only in B6-M76B mice, without affecting depressive-like behavior in both lines. In B6-M76B mice the behavioral alterations were accompanied by a decrease in the 5-HT2A receptor functional activity and the augmentation of levels of serotonin and its main metabolite, 5-HIAA (5-hydroxyindoleacetic acid), in the midbrain. Moreover, the levels of dopamine and its main metabolites, HVA (homovanillic acid) and DOPAC (3,4-dihydroxyphenylacetic acid), were also elevated in the striatum of B6-M76B mice after BDNF treatment. In B6-M76C mice, central BDNF administration led only to a reduction in the functional activity of the 5-HT1A receptor and a rise in DOPAC levels in the midbrain. The obtained data suggest the importance of the 102.73–118.83 Mbp fragment of mouse chromosome 13, which contains the 5-HT1A receptor gene, for BDNF-induced alterations in behavior and the brain monoamine system

    The effect of divergent selection on adrenocortical activity in Large White pigs on gene expression after ACTH, LPS and social stress challenges

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    The effect of divergent selection on adrenocortical activity in Large White pigs on gene expression after ACTH, LPS and social stress challenges. E. Terenina1, C. DuguĂ©1, E. Kulikova2, D. Bazovkina2, L. Gress1, G. Lefort1, Y. Billon3, C. Larzul1 & P. Mormede1 1 GenPhySE, INRA, INPT, ENSAT, UniversitĂ© de Toulouse, 31326 Castanet-Tolosan, France [email protected] (Corresponding Author) 2 Department of Behavioral Neurogenomics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia 3 GenESI, INRA, Le Magneraud, 17700 Surgères, France The objective of the present experiment is to analyze the expression of candidate genes related to HPA axis and stress in the third generation of selection of two lines of pigs divergently selected on the basis of plasma cortisol levels measured one hour after injection of ACTH. This test allows to objectify the activity level of the hypothalamic-pituitary-adrenal (HPA) axis, a major neuroendocrine system of the stress response. The kinetics of the blood transcriptomic responses to adrenocorticotropic hormone (ACTH), lipopolysaccharide (LPS) and social stress were measured at 4 time points (0, 1h, 4h, and 24h after the challenge). Our results suggest that the responses to these different challenges are not affected in the same way by HPA axis activity. We found 22 differentially expressed genes for the inflammatory stress, 2 genes specific to the response to ACTH injection and 12 genes for the social stress. The expression of studied candidate genes did not differ according to the line. Four genes (MEGF9, S100A9, CERS4 and PSAP) were found to be differentially expressed in the three tests and could therefore be used for the overall study of stress response. With the financial support of the Agence Nationale de la Recherche, program ANR BIOADAPT, project SUSoSTRESS (ANR-12-ADAP-0008)

    Time course study of the response to LPS targeting the pig immune gene networks

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    Background: Stress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. Results: Cortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t = +4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t = +1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response. Conclusions: The present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs
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