DHA (docosahexanenoic acid; 22:n-3) is an omega-3 long-chain polyunsaturated fatty acid recognized as being essential for normal neural development. Manipulating brain DHA levels during gestation and early development influences neural activity and behavior at maturity. Some, but not all, of these alterations are reversed when DHA is added to the diet at weaning.
In these figures, 'Replete' (blue) refers to a diet in which normal levels of alpha-linolenic acid are provided. 'Deficient' (red) is the diet with essentially no alpha-linolenic acid available. The 'Remediated' diet (green) is the deficent formulation with 3.4% DHA added - this diet was provided beginning at weaning (P21). Testing began on P56.
Click on a thumbnail image below to view a larger photo.
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Sometimes it's easier to explain using a diagram - this figure shows the experimental design and the timing of the diet manipulations in relation to testing. |
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Whole-brain lipid composition was determined for littermates culled at A) P1 and B) P21, and compared to C) Adult values from brains of the control & experimental rats after conclusion of all testing. Here, the ratio DHA plotted against a related fatty acid, docosapentaenoic acid (DPA; 225n-3) is shown. Addition of DHA to the deficient diet at weaning reverses an abnormally low level of brain DHA, but also normalizes the abnormally high levels of DPA in these rats. |
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Central neural activity evoked by flashes of light at A) 540x10^4 lux and B) 20x10^4 lux. The responses of rats with low brain DHA levels ('deficient diet') were larger than those fed a diet ('replete') that produced higher levels of brain DHA. This effect was particularly noticable at lower stimulus intensities. Addition of DHA to the deficient diet at weaning reversed these effects ('remediation'). |
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Central neural activity elicited by an auditory stimulus also is elevated when brain DHA levels are low but, by contrast to visual responses, auditory responses remain increased even after remediation with dietary DHA provided at weaning. |
DHA is a long-chain polyunsaturated fatty acid, and therefore is vulnerable to damage by free radicals. Cyclic exposure to changing oxygen levels increases the possibility of producing oxygen free radials, which in turn may damage the retina itself, or may produce neovascularization through activation of the VEGF pathway. One possibility is that a surfeit of circulating DHA may buffer against effects of elevated free radials. Another possibility is that exposure of excess DHA to free radicals may lead to lipid peroxidation and thus to more extensive damage in the lipid-rich retinal photoreceptors. These possibilities were evaluated by feeding pregnant rats diets that produce low, normal, or high levels of DHA, then exposing the newborn offspring to either room air or to an atmosphere that cycled daily for the first two weeks of life, from 50% oxygen available for 24 hours to 10% oxygen available for the next 24 hours. At 14 days of age, the rats were returned to room air. At 18 - 20 days of age, the retinal vasculature and the retinal fatty acids were examined.
This poster (downloads a 22MB .pdf file) discusses initial findings related the interaction of DHA availability and oxygen history. (presented at the 2005 Association for Research in Vision & Ophthalmology annual meeting)
This work suggests that dietary fatty acids have little direct effect on neovascularization, but that cyclic variations in oxygen levels does reduce the DHA content of the retina. In these rats, normal levels of retinal DHA are maintained only in rats fed a diet high in DHA. The combination of these preliminary findings suggests a neutral role for DHA supplementation of diets fed to very low birth weight human infants who also require oxygen supplementation in relation to neovascularization of the reitna (retinopathy of prematurity), but a beneficial role for maintaining normal levels of retinal DHA, and thus better visual acuity for those infants who do not progress to end stage ROP.
This poster (downloads a 13MB .pdf file) discusses findings related to the interaction of DHA availablity, oxygen history, and the presence of supplemental dietary iron during the early postnatal period. (presented at the 2005 Society for Free Radicals in Biology and Medicine annual meeting)
Current infant formulae often are supplemented with iron as well as other trace nutrients, including the recent addition of essential fatty acids. These findings show the deleterious effect of high iron levels in the diet when cyclic variations in oxygen levels are present, presumably leading to increased presence of oxygen free radicals. Low or moderate levels of DHA did not appear to alter the severity of the oxygen-induced vascular pathology irrespective of the presence or absence of iron. On the other hand, we have yet to determine if the severity of pathology associated with the interaction of oxygen and iron is diminished when high (4%) dietary DHA is available....