title: Early life iron deficiency impairs spatial cognition in neonatal piglets.
abstract: Iron deficiency is common throughout the world and has been linked to cognitive impairments. Using neonatal piglets to model human infants, we assessed the impact of iron deficiency on spatial learning and memory. Artificially reared piglets were fed 1 of 3 liquid diets with varying concentrations of iron: control (CON), mildly deficient (MID), or severely deficient (SID; 100, 25.0, or 10.0 mg iron/kg milk solids, respectively) for 4 wk. Relative to CON, SID and MID piglets had reduced hemoglobin (P < 0.05) as well as magenta skin color (P < 0.001), which correlated with hematocrit (R(2) = 0.76; P < 0.001). SID and MID hemoglobin differed at wk 3 and 4 (P < 0.05). In a hippocampal-dependent, spatial, T-maze task, SID piglets were unable to acquire the task (post hoc contrast: first vs. last day of acquisition), while MID piglets demonstrated deficits in reversal learning (P = 0.032). Iron concentrations in the liver (P < 0.001), serum (P = 0.003), and hippocampus (P = 0.004), but not prefrontal cortex, were lower in MID and SID compared with CON piglets. The level of the transferrin receptor mRNA (TFR) was greater in the prefrontal cortex of CON piglets than in MID and SID piglets (P = 0.001) but not the hippocampus. Gene expression of several neurotrophic factors and proinflammatory cytokines, as well as whole-brain and hippocampal volume, were not affected by dietary treatment. In conclusion, neonatal iron deficiency leads to cognitive impairment, which may be due in part to a reduced iron concentration in the hippocampus.
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rytych
authors.forename: Monica R P
authors.initials: MR
authors.lastname: Elmore
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burton
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Conrad
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Donovan
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Dilger
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000662:veterinary*; D000821:Animal Feed; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000662:veterinary*; D060888:Real-Time Polymerase Chain Reaction; D012880:Skin Pigmentation; D013037:Spatial Behavior; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy*
chemical_list: D009414:Nerve Growth Factors