Combined deficiency of iron and (n-3) fatty acids in male rates disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone

J. Baumgartner, C.M. Smuts, L. Malan, M. Arnold, B.K. Yee, L.E. Bianco, M.V. Boekschoten, M.R. Muller, W. Langhans, R.F. Hurrell, M.B. Zimmermann

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15 Citations (Scopus)

Abstract

Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21–56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70–76% and Fe by 20–32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P <0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P <0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P <0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P <0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.
Original languageEnglish
Pages (from-to)1463-1471
Number of pages9
JournalThe Journal of Nutrition
Volume142
Issue number8
DOIs
Publication statusPublished - 2012

Keywords

  • serotoninergic neurotransmission
  • working-memory
  • early-life
  • dopamine
  • oligodendrocytes
  • supplementation
  • myelination
  • impairment
  • expression
  • nutrition

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