Providing male rats deficient in iron and n3 fatty acids with iron and alpha linolenic acid alone affects brain serotonin and cognition differently from combined provision
Providing male rats deficient in iron and n3 fatty acids with iron and alpha linolenic acid alone affects brain serotonin and cognition differently from combined provision
Year: 2014
Authors: Baumgartner, J. Smuts, C.M. Zimmermann, M.B.
Publication Name: Lipids Health Dis.
Publication Details:
Abstract:
We recently showed that a combined deficiency of iron (ID) and n3 fatty acids (n3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n3 FAD alone. Providing these double deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double deficiency. Iron is a cofactor of the enzymes responsible for the conversion of alpha linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double deficient rats than ALA alone. In this study we examined whether providing double deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double deficiency. Using a 2 by 2 design, male rats with concurrent ID and n3 FAD were fed an Fe plus ALA, Fe plus n3 FAD, ID plus ALA, or ID plus n3 FAD diet for 5 weeks. Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age matched controls. In the hippocampus, we found a significant Fe by ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe plus ALA group. In the brain, we found significant antagonistic Fe by ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. These results indicate that providing either iron or ALA alone to double deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA. (Authors abstract)
Children and adolescents from low income countries may suffer from both, iron (Fe) deficiency (ID) and n3 fatty acid deficiency (n3 FAD) due to poor quality diets during periods of rapid growth. These researchers have shown in male rats that ID and n3 FAD in combination impairs monoaminergic neurotransmission and reference memory in the Morris water maze (MWM) to a greater extent than ID or n3 FAD alone. Approximately 35 percent of brain lipids occur in the form of polyunsaturated FA, with arachidonic acid (ARA; 20:4n6) and DHA being the main contributors. ALA makes up less than 1 percent of the brain’s lipids and may be crucial for brain development and functioning via its conversion to EPA and DHA. This might be particularly the case in human populations who do not consume fish and who do not have access to, or cannot afford fish oil supplements. In these populations improving DHA and EPA status by increasing the consumption of ALA rich oils (e.g. flaxseed, canola, and soybean oils) might be a more suitable approach. The provision of ALA in combination with Fe might be more effective in repleting brain EPA and DHA concentrations, and in reversing the deficits associated with n3 FAD, than the provision of ALA alone, particularly in ID subjects. Therefore, the aim of this study was to investigate whether repleting double deficient rats with ALA and Fe, alone or in combination, can correct deficits in brain monoamine metabolism and cognition associated with deficiency. The experimental model was chosen to reflect the common scenario in low income countries where children born to mothers with poor n3 FA status consume a diet low in Fe and n3 FA throughout childhood and only begin to consume a diet sufficient in one or both nutrients in early adulthood as dietary quality and variety improves. The provision of ALA to ID plus n3 FAD rats for 5 weeks significantly increased the relative composition of DHA in total phospholipid FA of different brain regions to 50 to 70 percent of control values. In contrast, the provision of Fe resulted in near complete recovery of brain Fe (90 to100 percent of controls. Thus, providing ALA in combination with Fe to double deficient rats might enhance the conversion of ALA into its respective long chain derivative DHA. Whether this finding can be translated to the human situation is not clear, as previous studies have shown that, in contrast to humans, the conversion of ALA to EPA and DHA is more efficient in rats.
These investigators demonstrated that rats repleted with ALA or Fe alone showed no learning effect in the reference memory task, indicated by a lack of improvement in distance swum across trials and days to find the hidden platform. On the other hand, rats that received ALA in combination with Fe exhibited a marked improvement. Consistent with their previous study in which a mixture of DHA/EPA was provided, alone and in combination with Fe, feeding either ALA or Fe alone to adult rats with both ID and n3 FAD affected brain 5HT concentrations differently from the provision of ALA and Fe in combination, and even exacerbated the working memory deficits associated with combined deficiency. The provision of ALA had a beneficial effect on reference memory, particularly when provided in combination with Fe, which may be explained by the enhancing effect of Fe on the conversion of ALA to DHA in the Hip. These findings are of relevance to human populations, as many children from a low socioeconomic background may suffer from both ID and n3 FAD due to poor quality diets. Furthermore, in populations with a low fish intake, improving DHA and EPA status by increasing the consumption of ALA rich oils (e.g. flaxseed, canola or soybean oils) might be a more suitable approach. The results indicate that in such populations, it may be crucial to provide ALA rich oils and foods in combination with Fe. (Editors comments)
