title: Prenatal choline supplementation ameliorates the long-term neurobehavioral effects of fetal-neonatal iron deficiency in rats.
abstract: BACKGROUND
  Gestational iron deficiency in humans and rodents produces long-term deficits in cognitive and socioemotional function and alters expression of plasticity genes in the hippocampus that persist despite iron treatment. Prenatal choline supplementation improves cognitive function in other rodent models of developmental insults.
  
  
  OBJECTIVE
  The objective of this study was to determine whether prenatal choline supplementation prevents the long-term effects of fetal-neonatal iron deficiency on cognitive and social behaviors and hippocampal gene expression.
  
  
  METHODS
  Pregnant rat dams were administered an iron-deficient (2-6 g/kg iron) or iron-sufficient (IS) (200 g/kg iron) diet from embryonic day (E) 3 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline chloride, E11-18). Novel object recognition (NOR) in the test vs. acquisition phase, social approach (SA), and hippocampal mRNA expression were compared at P65 in 4 male adult offspring groups: formerly iron deficient (FID), FID with choline supplementation (FID-C), IS, and IS with choline supplementation.
  
  
  RESULTS
  Relative to the intact NOR in IS rats (acquisition: 47.9%, test: 60.2%, P < 0.005), FID adult rats had impaired recognition memory at the 6-h delay (acquisition: 51.4%, test: 55.1%, NS), accompanied by a 15% reduction in hippocampal expression of brain-derived neurotrophic factor (Bdnf) (P < 0.05) and myelin basic protein (Mbp) (P < 0.05). Prenatal choline supplementation in FID rats restored NOR (acquisition: 48.8%, test: 64.4%, P < 0.0005) and increased hippocampal gene expression (FID-C vs. FID group: Bdnf, Mbp, P < 0.01). SA was also reduced in FID rats (P < 0.05 vs. IS rats) but was only marginally improved by prenatal choline supplementation.
  
  
  CONCLUSIONS
  Deficits in recognition memory, but not social behavior, resulting from gestational iron deficiency are attenuated by prenatal choline supplementation, potentially through preservation of hippocampal Bdnf and Mbp expression. Prenatal choline supplementation may be a promising adjunct treatment for fetal-neonatal iron deficiency.
authors.affiliation: Graduate Program in Neuroscience, Center for Neurobehavioral Development, Kenne379@umn.edu.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Kennedy
authors.affiliation: Department of Psychology.
authors.forename: Jiva G
authors.initials: JG
authors.lastname: Dimova
authors.affiliation: Center for Neurobehavioral Development, Department of Pediatrics, and.
authors.forename: Asha J M
authors.initials: AJ
authors.lastname: Siddappa
authors.affiliation: Center for Neurobehavioral Development, Department of Pediatrics, and.
authors.forename: Phu V
authors.initials: PV
authors.lastname: Tran
authors.affiliation: Graduate Program in Neuroscience, Center for Neurobehavioral Development, Department of Psychology.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Gewirtz
authors.affiliation: Graduate Program in Neuroscience, Center for Neurobehavioral Development, Department of Pediatrics, and Institute of Child Development, University of Minnesota, Minneapolis, MN.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002794:Choline / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation; D006400:Hematocrit; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000090463:Iron Deficiencies; D019266:Iron, Dietary; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008568:Memory / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
chemical_list: D019266:Iron, Dietary; D002794:Choline