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INVOLVEMENT OF TISSUE-TYPE PLASMINOGEN ACTIVATOR IN THE REGULATION OF CIRCADIAN RHYTHMS

Linley, Moreland
http://rave.ohiolink.edu/etdc/view?acc_num=kent1278950189

Abstract Details

2010, MS, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Tissue-type plasminogen activator (tPA), a serine protease traditionally known for its regulation of fibrinolytic activity in the bloodstream, is also responsible for generation of mature brain-derived neurotrophic factor (mBDNF) in the central nervous system. Since mBDNF is critical to photic entrainment and normal phase-shifting behavior in the suprachiasmatic nucleus (SCN), we monitored the circadian phase shift response to light during early and late subjective night in mice deficient in tPA (tPAKO) in comparison to wildtype (WT) mice. tPAKO mice did not exhibit differential phase-shifting behavior during early or late subjective night in comparison to WT mice. To assess whether entrainment to food was altered in the knockout mice, tPAKO and WT mice were put on a restricted feeding schedule on a light-dark cycle to monitor the behavioral response to a nonphotic cue as well as expression of food anticipatory activity (FAA). Since tPAKO mice are deficient in long-term potentiation and memory, we hypothesized that tPAKO mice would show decreased FAA as the animals would have difficulty learning the time of food restriction. Contrary to our hypothesis, tPAKO mice exhibited significantly enhanced FAA in comparison to WT mice, which gradually decreased over a span of 10 days. The locomotor activity of tPAKO and WT mice were also monitored during a 48hr fast. Since no significant difference in activity between genotypes was observed during the 48hr fast, it appears that the enhanced FAA of tPAKO mice is specific to the restricted feeding schedule and not just a result of reduced food availability. Expression of central and peripheral clock genes in the SCN and liver of tPAKO and WT mice were assayed during the phase of FAA (ZT5). Clock was suppressed in the liver during restricted feeding in both genotypes, while Per1 and Per2 were increased. Per2 expression was also significantly higher in tPAKO mice than WT mice during restricted feeding. In the SCN, there was no significant difference in Per1 and Per2 expression between genotype or feeding regimen, consistent with previous reports of SCN activity being unaffected by a restricted feeding regimen. A significant interaction was observed in that Clock expression was significantly higher in WT mice than tPAKO mice during ad libitum feeding. The present data clearly indicate a role for tPA modulation of FAA, and further research will be necessary to identify the mechanisms through which tPA modulates central structures and influences peripheral feedback during restricted feeding.
Eric Mintz (Advisor)
Heather Caldwell (Committee Member)
Sean Veney (Committee Member)
Biology
tissue-type plasminogen activator; food anticipatory activity; food restriction; circadian

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Citations

  • Linley, M. (2010). INVOLVEMENT OF TISSUE-TYPE PLASMINOGEN ACTIVATOR IN THE REGULATION OF CIRCADIAN RHYTHMS [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1278950189

    APA Style (7th edition)

  • Linley, Moreland. INVOLVEMENT OF TISSUE-TYPE PLASMINOGEN ACTIVATOR IN THE REGULATION OF CIRCADIAN RHYTHMS. 2010. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1278950189.

    MLA Style (8th edition)

  • Linley, Moreland. "INVOLVEMENT OF TISSUE-TYPE PLASMINOGEN ACTIVATOR IN THE REGULATION OF CIRCADIAN RHYTHMS." Master's thesis, Kent State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1278950189

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Kent State University and OhioLINK.