The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.
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Michael K. Georgieff, MD
Department of Pediatrics
D-136 Mayo Building, MMC 39, 420 Delaware St. SE Minneapolis, MN 55455 (USA)
Tel. +1 612 626 0644, Fax +1 612 624 8176, E-Mail firstname.lastname@example.org
Received: February 23, 2010
Accepted after revision: April 26, 2010
Published online: August 6, 2010
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 2, Number of References : 51
Vol. 32, No. 3, Year 2010 (Cover Date: August 2010)
Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)
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