Search

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 x 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 memony performance was Impaired in ID+DHA/EPA rats compared with controls (P< 0.05). In the reference memory task, Fe-i-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. [ABSTRACT FROM AUTHOR]

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 X 2 design, male rats were fed an ID, (n-3)FAD, ID-t-(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 olfactor/ bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID-r(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID-r(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-H(n-3)FAD rats (fold-change = -1.33; P<0.05). ID and (n-3)FAD significantly impaired working memon/ performance and the impairment positively correlated with DA concentrations in FC (r= 0.39; P= 0.026). Reference memor/ 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. [ABSTRACT FROM AUTHOR]