ObjectiveTo study the effect of superparamagnetic iron oxide nanoparticles (SPION) by intracerebroventricular adiministration on the locomotor circadian rhythm in mice. MethodsSix-week-old male C57BL mice were maintained on a 12h light (200lux)-12h dark cycle for 14 days with free access for food and water, then the animals were put into constant darkness (DD) for another 14 days, followed by the start of running wheel monitoring under DD condition. SPION (4μl) was intracerebroventricularly injected (i.c.v.) at CT (circadian time) 14 and monitoring of the running wheel activitied was continued for different time periods. Animals were sacrificed after 10 min, 24h, 14d, or 30d, respectively. Brain tissues were developed and brain paraffin sections were stained with prussian blue to identify the location of SPION. Clock genes were detected by real time-RT-qPCR. ResultsWithin 24h after SPION injection, the SPION were attached to the cerebral ventricle walls, but were not observed inside the neuronal cells. However, SPION were observed entering into the neuronal cells 14d after the injection. In addition, a phase delay of the circadian rhythm of the locomotor activities was observed in the SPION injected group compared with the placebo-injected animals. The locomotor activity of mice circadian rhythm changed. The mRNA levels of per1 and per2 in the SCN were significantly elevated in the SPION treated animals while unchanged in the control animals. ConclusionSPION can enter into the neuronal cells after i.c.v. administration and affected the circadian rhythm of locomotor activities in mice. These effects are associated with the alterations of the per1 and per2 transcriptions in the SCN.