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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Physiology 1/2018

Regulation of Locomotor activity in fed, fasted, and food-restricted mice lacking tissue-type plasminogen activator

BMC Physiology > Ausgabe 1/2018
Jessica A. Krizo, Linley E. Moreland, Ashutosh Rastogi, Xiang Mou, Rebecca A. Prosser, Eric M. Mintz
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12899-018-0036-0) contains supplementary material, which is available to authorized users.



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.
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