Docosahexaenoic acid (DHA, 22 : 6n-3), an essential n-3 polyunsaturated fatty acid, is one of the integral components of neural membrane phospholipids and is essential for normal neurological development and vision. DHA deficiency markedly affects neurotransmission, activities of membranebound enzymes and ion channel, gene expression and synaptic plasticity; it is thus associated with some neurological dysfunction in aging, Alzheimer's disease (AD), depression and peroxisomal disorders. Deficiency in dietary DHA induces loss of discriminative learning ability; thus intake of DHA may restore this loss. Epidemiological studies show a relation between the ingestion of fish oils and AD, suggesting neuroprotective consequences of the oil, especially of DHA. Although the molecular mechanism of DHA involvement in neurological disorders remains unknown, dietary administration of DHA improves lost learning ability in animals, and protects against and ameliorates the impairment of learning ability in AD model rats and mice. The improvement effect of dietary DHA on memory/learning ability and its application to AD and depression in neurological dysfunction is reviewed here.

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Docosahexaenoic acid (DHA), a long chain fatty acid of n-3 series, is highly enriched in the membrane phospholipids of the retina as well as brain and neuronal tissues. Loss of DHA because of n-3 deficiency is associated with visual deficits as observed in animal and human infants study. How is DHA related to retinal structure and function? Recent research provided the evidence that rod outer segment (ROS) from n-3 fatty acid-deficient rats showed desensitization of the visual signaling steps in a G protein-coupled receptor signal transduction. ROS membranes from n-3 deficient rats exhibited a higher degree of phospholipids acyl chain order. Thus, DHA may operate in signaling cascades to enhance activation of membrane-bound receptors and subsequent signaling events by optimizing biophysical membrane properties. DHA may also be involved in rhodopsin regeneration. On the other hand, DHA-derived neuroprotective mediator was isolated from human retinal pigment epithelial cells and identified as 10, 17S-docosatriene named neuroprotectin Dl. In conclusion, there is consistent evidence to suggest that n-3 fatty acids may act in a pivotal role for the visual signaling and a protective role against pathology of retina such as retinitis pigmentosa.

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Marine Vitamins are biologically active substances from marine resources for human health. Especially DHA, Astaxanthin and Phosphatidylserine (PS) as marine vitamin, are known as Brain Foods those have an ability of improvement of brain function.
Many double-blind randomized control clinical studies of PS show the activity of improvement of senile dementia, anteriosclerotic encephalopathy, senile mental deterioration, age-associated memory impairment and Alzheimer's disease.

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Because N-Methyl-D-aspartate (NMDA) type glutamate receptor has been considered to be involved in the higher brain functions such as learning and memory, facilitating effects of glycine, D-serine and D-alanine on the NMDA receptor-mediated transmission are expected to ameliorate a variety of neuropsychiatric disorders. However, the low ability of these polar amino acids to cross through the blood-brain barrier (BBB) would be a serious disadvantage in their systemic administration for the clinical application. Indeed, extremely large doses of glycine and D-serine have been reported to be required to attenuate schizophrenic symptoms. To overcome this disadvantage through increasing the fat solubility of D-serine, the authors designed and synthesized N-acyl D-serine and evaluated its permeability of the BBB by testing in the rat the effects of the N-acyl compound on abnormal behavior induced by a potent NMDA antagonist chizophrenomimetic, phencyclidine, which is thought to be a model of schizophrenia. Intraperitoneal injection of the N-acyl D-serine attenuated the phencyclidine-induced abnormal behavior and this attenuation was diminished by intraventricular application of a selective antagonist for the glycine modulatory site of the NMDA receptor at which D-serine acts as a selective agonist. These data support the BBB permeability of the acyl D-serine and suggest that certain fat soluble amino acids could be useful for the treatment of neuropsychiatric disorders.

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