title: 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.
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.
authors: Laboratory of Human Nutrition, ETH, 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 / Q000378:metabolism*; D004032:Diet / Q000662:veterinary; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; 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