Background: Decreases in female hormones not only affect bone metabolism and decrease bone mass,
but also affect the central nervous system, causing brain disorders such as depression and dementia. Administration
of estradiol by hormone replacement therapy can improve dementia, while reduced estradiol in ovariectomized
(OVX) model rats can reduce both bone density and locomotor activity. The antidepressant fluvoxamine, which is
widely used in clinical practice, can improve this effect on locomotor reduction. Similarly, lactoferrin (LF) can
reportedly improve inhibitory locomotion due to stress.
Objective: In this study, we examined the effect of LF on neurite outgrowth in vitro and in vivo using PC12 cells and
Methods: We performed an in vivo study in which 8-week-old female OVX rats were administered LF five days a
week for 6 weeks from the day after surgery. After administration was completed, spontaneous locomotor activity in
the dark period, immobility time in a forced swim test, and release amount of dopamine and serotonin in the brain
Results: LF was found to have a neurite outgrowth function in PC12 cells. Moreover, LF was found to improve
OVX-induced decreases in locomotor activity and increases in immobility time in the forced swim test. Furthermore,
administration of LF elicited significant recovery of decreased dopamine and serotonin release in the brains of OVX
Conclusion: These results strongly suggest that LF improved OVX-induced decreases in momentum during the dark
period and, moreover, that release of dopamine and serotonin in the brain was involved in this effect.