This study investigated the influence of brain docosahexaenoic acid (DHA) deficiency on simple and complex olfactory-based learning and memory in 2nd generation (F2) adult male rats. Rats raised and maintained on either an n-3-adequate or an n-3-deficient diet were tested for acquisition of an olfactory learning set and an olfactory memory task, and for motivation to obtain a water reward. Despite a 76% decrease in brain DHA, n-3-deficient rats were able to acquire most simple 2-odor discrimination tasks but were deficient in the acquisition of a 20-problem olfactory learning set. This deficit could not be attributed to changes in sensory capacity but, instead, appeared to represent a deficit in higher order learning.

The concentration of the major polyunsaturated fatty acid (PUFA) in brain, docosahexaenoate, may be markedly reduced by two or more generations of dietary restriction of sources of n-3 fatty acids in the diet. Such a deficiency was induced through the feeding of safflower oil as the principal source of essential fatty acids. The reference point for this diet was an n-3 adequate diet to which alpha-linoleate and docosahexaenoate were added through the addition of a small quantity of flax seed or algael oils, respectively. The loss of brain DHA was associated with poorer performance in spatial tasks and an olfactory-cued reversal learning task. No difference could be observed in the hippocampal gross morphology. This study demonstrates the importance of providing a source of n-3 fatty acids during mammalian growth and development.

The reciprocal replacement of DHA by docosapentaenoic acid (DPAn-6) was studied in rats that consumed an n-3 FA-deficient or n-3 FA-adequate diet. Dams were fed the two experimental diets from weaning and throughout pregnancy and lactation. Their pups were then fed the respective diets after weaning. Cortex FA analysis was performed at various times (0, 5, 10, 20, 50, and 91 d) after birth to determine whether DPAn-6 completely replaced DHA in the n-3-deficient group. Cortical DHA levels were significantly lower (average 86%) in the n-3-deficient rats. DPAn-6 increased significantly in the n-3-deficient rats starting with a 6.5-fold increase at day 0 up to a 54-fold increase at day 91 compared with the n-3-adequate group. However, this significant increase did not completely replace the loss of DHA at postnatal days 5, 10, and 20 in which there was still an 11.5, 10.3, and 8.0% deficit in the sum of DHA and DPAn-6, respectively, in the n-3-deficient group. Once docosatetraenoic (DTA) and arachidonic acids (AA) were included in the sum (DHA + DPAn-6 + DTA + AA), the levels between the two groups were similar. These results suggest that not only DPAn-6 but also other n-6 FA, including DTA and AA, replace DHA in n-3-deficient rats. The lack of total 22-carbon (22C) FA in the brain during the rapid membrane biogenesis that occurs during early development could be a factor in the nervous system functional deficits associated with n-3 FA deficiency.

The loss of docosahexaenoic acid (DHA) from the retina or brain has been associated with a loss in nervoussystem function in experimental animals, as well as in human infants fed vegetable oil-based formulas. The reversibility of the loss of DHA and the compensation by an increase in the n-6 docosapentaenoic acid (DPAn-6) was studied in young adult rats. Long-Evans rats were subjected to a very low level of n-3 fatty acids through two generations. The F2 generation, n-3-deficient animals at 7 weeks of age were provided a repletion diet containing both ␣ -linolenate and DHA. A separate group of F2 generation rats had been maintained on an n-3-adequate diet of the same composition. Tissues from the brain, retina, liver, and serum were collected on weeks 0, 1, 2, 4, and 8 from both groups of animals. The concentrations of DHA, DPAn-6, and other fatty acids were determined and the rate of recovery and length of time needed to complete DHA recovery were determined for each tissue. The DHA level in the brain at 1 and 2 weeks after diet reversal was only partially recovered, rising to approximately 20% and 35%, respectively, of the n-3-adequate group level. Full recovery was not obtained until 8 weeks after initiation of the repletion diet. Although the initial rate of retinal DHA accretion was greater than that of brain DHA, the half-time for DHA recovery was only marginally greater. On the other hand, the levels of DHA in the serum and liver were approximately 90% and 100% replaced, respectively, within 2 weeks of diet reversal. A consideration of the total amounts and time courses of DHA repleted in the nervous system compared with the liver and circulation suggests that transport-related processes may limit the rate of DHA repletion in the retina and brain. -Moriguchi, T., J.