title: In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.
abstract: Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.
authors: Laboratory of Human Nutrition, ETH Zurich, Zurich, Switzerland. jeannine.baumgartner@gmail.com
authors: Jeannine
authors: J
authors: Baumgartner
authors: Cornelius M
authors: CM
authors: Smuts
authors: Linda
authors: L
authors: Malan
authors: Myrtha
authors: M
authors: Arnold
authors: Benjamin K
authors: BK
authors: Yee
authors: Laura E
authors: LE
authors: Bianco
authors: Mark V
authors: MV
authors: Boekschoten
authors: Michael
authors: M
authors: Müller
authors: Wolfgang
authors: W
authors: Langhans
authors: Richard F
authors: RF
authors: Hurrell
authors: Michael B
authors: MB
authors: Zimmermann
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004032:Diet / Q000662:veterinary; D019587:Dietary Supplements / Q000009:adverse effects; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007501:Iron / Q000008:administration & dosage*; D000090463:Iron Deficiencies; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000378:metabolism*; D010743:Phospholipids; D040081:Protein Array Analysis; D011897:Random Allocation; D051381:Rats
chemical_list: D015306:Biogenic Monoamines; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; D007501:Iron