Krizo Jessica A, Moreland Linley E, Rastogi Ashutosh, Mou Xiang, Prosser Rebecca A, Mintz Eric M
Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
BMC Physiol. 2018 Jan 25;18(1):2. doi: 10.1186/s12899-018-0036-0.
Circadian rhythms of physiology and behavior are driven by a circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This clock is synchronized to environmental day/night cycles by photic input, which is dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from plasminogen by the enzyme tissue-type plasminogen activator (tPA). In this study, we evaluate circadian function in mice lacking functional tPA.
tPA mice have normal circadian periods, but show decreased nocturnal wheel-running activity. This difference is eliminated or reversed on the second day of a 48-h fast. Similarly, when placed on daily cycles of restricted food availability the genotypic difference in total wheel-running activity disappears, and tPA mice show equivalent amounts of food anticipatory activity to wild type mice.
These data suggest that tPA regulates nocturnal wheel-running activity, and that tPA differentially affects SCN-driven nocturnal activity rhythms and activity driven by fasting or temporal food restriction.
生理和行为的昼夜节律由位于下丘脑视交叉上核的生物钟驱动。该生物钟通过光输入与环境昼夜周期同步，而光输入依赖于视交叉上核中成熟脑源性神经营养因子（BDNF）的存在。成熟的BDNF由纤溶酶产生，纤溶酶由组织型纤溶酶原激活剂（tPA）将纤溶酶原转化而来。在本研究中，我们评估了缺乏功能性tPA的小鼠的昼夜节律功能。
tPA基因敲除小鼠有正常的昼夜周期，但夜间转轮活动减少。在48小时禁食的第二天，这种差异消除或逆转。同样，当置于每日食物供应受限的周期中时，总转轮活动的基因型差异消失，tPA基因敲除小鼠表现出与野生型小鼠等量的食物预期活动。
这些数据表明，tPA调节夜间转轮活动，并且tPA对视交叉上核驱动的夜间活动节律和禁食或限时进食驱动的活动有不同影响。
