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Docosahexaenoic acid (DHA), a 22-carbon, highly unsaturated, n-3 fatty acid, is important for optimal nervous system function. In this study, designed to quantify how preformed dietary DHA regulates metabolic pathways in vivo, 8-d-old rat pups were divided into four groups and fed artificial rat milk diets. One group was fed formula with deuterium-labeled LNA (d5-LNA) as the only source of n-3 fatty acids, and a second group was fed formula that contained d5-LNA and unlabeled DHA. Two additional groups were dam-reared to permit analysis of fatty acyl pool sizes at postnatal days 8 and 28. The dams were fed a diet that contained 3% unlabeled LNA. DHA in brain and liver was analyzed. Our study demonstrated that preformed DHA in the diet markedly decreased the amount of biosynthesized DHA that accumulated in the brain and the liver. Surprisingly, 40% of the DHA that was newly acquired during this period in the "LNA" group was unlabeled. Because there were no unlabeled n-3 fatty acids in this diet, this DHA must have been derived from body stores of n-3 fatty acids. Thus, body stores can be a significant source of brain DHA in animals that are fed LNA as the only source of n-3 fatty acids. Abbreviations AA, arachidonic acid DHA, docosahexaenoic acid d5-DHA, deuterium-labeled docosahexaenoic acid d5-LNA, deuterium labeled ␣-linolenic acid DPAn-6, docosapentaenoic acid EE, ethyl ester EPA, eicosapentaenoic acid GC, gas chromatography LCP, long-chain polyunsaturate LNA, ␣-linolenic acid MS, mass spectrometry Docosahexaenoic acid (DHA) is a 22-carbon, highly unsaturated, n-3 fatty acid that accumulates in high concentrations in the brain and the retina. It is known that DHA is important for optimal nervous system function as significant deficiency states are associated with decreased behavioral function in animal models (1-8). N-3 fatty acids are essential nutrients for mammals, that is, they cannot be synthesized de novo. However, longer chain n-3 fatty acids such as DHA can be biosynthesized in mammals from n-3 fatty acid precursors such as the 18-carbon n-3 fatty acid ␣-linolenic acid (LNA) (9 -13).An important question for essential fatty acid nutrition has been whether preformed dietary DHA is required or needs can be met with its precursor LNA. Although breast milk always contains DHA (14), until 2002, no infant formula that contained DHA was available in North America as n-3 fatty acids were supplied only in the form of LNA.Whether it is reasonable to expect metabolism of LNA to supply all of the DHA needed for brain and other organ growth remains unclear. Data from previous tracer studies show a marked neural tissue preference for preformed DHA over metabolized LNA during development (15,16). Furthermore, animals that ingest diets with high levels of LNA are unable to reach brain DHA levels of animals that ingest .This study therefore was designed to quantify the amount of brain and liver DHA derived from biosynthesis when preformed DHA was or was not available in the diet. It has been suggested that liver micro...

Neurons in the cerebral cortex are organized horizontally into laminae and vertically into columns and modules. Little is known about the structural variation of neuronal organization in the vertical (pia to white matter) dimension. We describe here a new computer-assisted methodology that quantifies the linear arrangement of cells and shows how cortical columns in a homologous region differ by species and age. Perikarya in eulaminate temporal cortex, Tpt, were segmented from the background on the basis of their optical densities and sizes in human, rhesus (Macaca mulatta), and chimpanzee (Pantroglodytes) brains. Within each lamina, the two-dimensional arrays of neurons were divided into repetitive, objectively defined vertical clusters. Following this, ratios and indices quantified the displacement of perikaryal centroids from the central axis and from the center point in each cell cluster. The extremely linear and vertical arrangement of cells in the prelaminated fetal cortical plate served as the template to which the other arrays were compared. In all species, the linear arrangements of perikarya in lamina III, and to a lesser extent, in lamina V, closely resemble that of the early fetal template, whereas perikaryal arrangements in layers II and IV diverge from the template formation. Corroborating subjective visualization, each lamina had its own 'fingerprint'. As expected, cell density is less in the species with larger brains, with most of the differences in density coming from increased spacing between cellular columns rather than among the cells within columns. Not all aspects of perik-aryal organization alter when bigger brains are compared with smaller ones. Although chimpanzee brains are about four times bigger than those of rhesus monkeys and human brains are about three times larger than chimpanzee brains, absolute measures of cellular linearity in chimpanzees and rhesus monkeys resemble each other more closely than the same measures do in humans and chimpanzees. After accounting for differences in interval widths, the parameters of linearity sorted on the basis of brain weight in pyramidal cell layers III and V, but not in the stellate cell layers II and IV. Human perikarya have the widest horizontal dispersion and this displacement is most pronounced in layer II, least in layer III.

Rat pups born to dams fed a diet with 3.1% of total fatty acids as ␣ -linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model. -Moriguchi, T., S-Y. Lim, R.