The effects of dietary iron deprivation on murine circadian sleep architecture

Objectives: Iron deficiency is considered a putative cause for restless legs syndrome (RLS), a human sensorimotor disorder characterized by a circadian presentation of symptoms during the evening hours that disrupts one's ability to sleep. We sought to evaluate the sleep-wake effects of diet-induced iron deficiency in mice as an animal model of RLS. To this end, we hypothesized that the iron-deprived mice would exhibit a sleep-wake circadian pattern characteristic of the human syndrome: increased wakefulness during the hours immediately preceding the sleep-predominant period. Methods: Following weaning at post-natal day (PND) 21, C57BL/6J mice were assigned to one of two dietary treatments: iron-deficient (ID, n = 7) or iron-adequate (i.e., control, CTL, n = 6). At PND 44, the mice were surgically instrumented for polysomnographic (PSG) recording, and data were collected at young adulthood: PNDs 59 and 60. Sleep-wake architecture was characterized for the 12-h light and dark periods and also for six consecutive 4-h blocks comprising a 24-h day. Results: The ID mice showed marked increases in wake time in the 4-h period prior to lights-on; both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were reduced. In contrast, sleep-wake activity did not differ across the 12-h light period. Conclusions: Dietary iron deficiency in mice elicited increases in wakefulness during a particular circadian time point that corresponds to the period during which RLS symptoms would maximally disturb sleep onset and progression in humans. These data indicate that iron-deficient mice may provide a potentially useful animal model for RLS.