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

BMC Physiol. 2018 Jan 25;18(1):2. doi: 10.1186/s12899-018-0036-0.


Background: 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.

Results: 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.

Conclusions: 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.

Keywords: Circadian; Food anticipatory activity; Wheel-running.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Circadian Clocks*
  • Circadian Rhythm*
  • Eating
  • Fasting
  • Food Deprivation
  • Locomotion*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Suprachiasmatic Nucleus / metabolism
  • Tissue Plasminogen Activator / genetics
  • Tissue Plasminogen Activator / physiology*


  • Brain-Derived Neurotrophic Factor
  • Tissue Plasminogen Activator