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

Jeannine Baumgartner, Cornelius M. Smuts, Linda Malan, Myrtha Arnold, Kay Yan Benjamin Yee, Laura E. Bianco, Mark V. Boekschoten, Michael Müller, Wolfgang Langhans, Richard F. Hurrell, Michael B. Zimmermann

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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 (bymeasuring monoamines and related gene expression) and spatial working and referencememory (by Morris watermaze testing). Using a 23 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 =21.33; P < 0.05). ID and (n-3)FAD significantly impairedworking memory performance and the impairment positively correlatedwith DA concentrations in FC (r = 0.39; P = 0.026). Referencememorywas impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r =20.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brainmonoamine 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
JournalJournal of Nutrition
Issue number8
Publication statusPublished - 1 Aug 2012
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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