The effects of dietary iron deprivation on murine circadian sleep architecture.
OBJECTIVE
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.
Dean
Terry
T
The University of Pennsylvania School of Medicine, Department of Neuroscience, USA. terrydeanjr@gmail.com
Allen
Richard P
RP
O'Donnell
Christopher P
CP
Earley
Christopher J
CJ
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D003677:Deficiency Diseases / Q000150:complications / Q000503:physiopathology; D004195:Disease Models, Animal; D000090463:Iron Deficiencies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017286:Polysomnography; D012148:Restless Legs Syndrome / Q000209:etiology* / Q000503:physiopathology; D012890:Sleep / Q000502:physiology