Effect of DHA deficiency on spatial learning behavior and antioxidant status in rat brain

Docosahexaenoic acid (DHA, 22-6n-3) and arachidonic acid (AA, 22:4n-6) are long-chain polyunsaturated fatty acids (LCPUFA), which are important for the structural development of mammalian central nervous system and are accumulated in large amounts in the developing brain, retina and sperm. Deficiency in DHA and AA syndromes can occur if these fatty acids and their precursors (linoleic and linolenic acid) are insufficient in diet. It had been reported that DHA deficiency in animal brain led to a poor performance in learning ability and other abnormal behavior in rodents. In addition, DHA and AA are the unique fatty acids in human milk. Many studies reported that children who were breast-fed got higher intelligent scores than those who were formula-fed. Thus, a large number of studies suggested that DHA and AA should be added into infant formula to mimic the composition of human milk.; The objectives of present study were to (1) examine the distribution, depletion and recovery of DHA in rat brain; (2) investigate the effect DHA deficiency in rat brain on spatial learning behavior; (3) study the effect of DHA deficiency on antioxidant enzymes in rat brain; and (4) analyze whether DHA and AA supplementation has any beneficial effect on cognitive development and quantify their effect size in children by conducting a meta-analysis of the published data, and adult rats, the region with the highest DHA percentage was cortex, whereas in aged rats, both cortex and cerebellum were the regions with the highest DHA percentage. DHA concentration in rat brain increased with age. DHA was not proportionally depleted and recovered in different regions of rat brain when the rats were maintained on an n-3 fatty acid deficient diet for two generations. The present results demonstrated that the distribution of DHA and AA was region-specific.; DHA depletion in brain was associated with impairment on spatial learning and memory in rat. The Morris water maze test found that the n-3 deficient rats spent more time and swam a longer distance to find the hidden platform compared with the n-3 adequate group, indicating that n-3 Def rats had a poorer spatial learning ability and memory. The results suggest that learning and memory are partially related to the brain DHA status in rat.; No significant relationship between DHA level and brain antioxidant enzyme activities was observed, including catalase (CAT), Cu-Zn superocide dismutase (Cu-Zn SOD), Mn superocide dismutase (Mn SOD) and glutathione peroxidase (GPx). These enzyme activities varied with regions of brain. A lower activity of CAT, Mn SOD and GPx in hippocampus and cortex would make them particularly susceptible to oxidation damage compared with other regions. The present results did not support the view that the spatial learning and memory impairment in DHA depletion was associated with antioxidant status in brain.; The meta-analysis indicated that breast-feeding was positively associated with a higher cognitive development than formula-feeding. However, no benefit was found for infants who received formula supplemented with DHA alone or DHA plus AA compared with those fed traditional formula based on available data. The results suggest that the beneficial effect of breast-feeding over formula-feeding can not be solely attributed to DHA and AA present in breast milk.; In summary, DHA distribution, depletion and recovery were region-specific in rat brain. DHA deficiency could lead to impairment on spatial learning in rat. The underlying mechanism of learning deficit might not be attributed to changes in antioxidant enzymes in rat brain. Although impairment on spatial learning was observed in DHA-deficient rat, a meta-analysis of published data demonstrated that DHA and AA supplement in infant formula had no effect on cognitive development in children.