Gestational and lactational iron deficiency alters the developing striatal metabolome and associated behaviors in young rats

Abstract

Gestational and early postnatal iron deficiency occurs commonly in humans and results in altered behaviors suggestive of striatal dysfunction. We hypothesized that early iron deficiency alters the metabolome of the developing striatum and accounts for abnormalities in striatum-dependent behavior in rats. Sixteen metabolite concentrations from a 9-11 microL volume within the striatum were serially assessed in 10 iron-deficient and 10 iron-sufficient rats on postnatal days 8, 22 (peak anemia), and 37 (following recovery from anemia) using (1)H NMR spectroscopy at 9.4 tesla. Chin-elicited bilateral forelimb placing and vibrissae-elicited unilateral forelimb placing were also assessed on these days. Iron deficiency altered metabolites indexing energy metabolism, neurotransmission, glial integrity, and myelination over time (P < 0.05). Successful development of behaviors was delayed in the iron-deficient group (P < or = 0.01). Alterations in creatine, glucose, glutamine, glutamate, N-acetylaspartate, myo-inositol, and glycerophosphorylcholine + phosphorylcholine concentrations accounted for 77-83% of the behavioral variability during peak anemia on postnatal day 22 in the iron-deficient group. Correction of anemia normalized the striatal metabolome but not the behaviors on postnatal day 37. These novel data imply that alterations in the metabolite profile of the striatum likely influence later neural functioning in early iron deficiency.

Figure 1

Sagittal and coronal MRI, and ¹H NMR spectra of the iron-deficient striatum. ¹H NMR spectra were obtained from a 9-11 μL volume of the striatum (boxes in MRI) on P8 (A), P22 (B), and P37 (C). Ala, alanine; Asc, ascorbate; Asp, aspartate; Cr, creatine; GABA, γ-aminobutyric acid; Glc, glucose; Glu, glutamate; Gln, glutamine; GPC, glycerophosphorylcholine; Lac, lactate; Ins, myo-inositol; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; PCr, phosphocreatine; PCho, phosphorylcholine; PE, phosphorylethanolamine; Tau, taurine.