Abstract
Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid (PUFA) critical for maintaining normal brain structure and function, and is considered neuroprotective. Its brain concentration depends on dietary DHA content and its hepatic conversion from its nutritionally essential n-3 precursor, α-linolenic acid (ALA). We have developed an in vivo method in rats using quantitative autoradiography and intravenously injected radiolabeled DHA to image net DHA incorporation into the brain of unesterified plasma DHA. Using this method, the incorporation rate, Jin(DHA), equals the rate of brain metabolic DHA consumption, whereas the incorporation coefficient k* represents a lumped affinity of brain for plasma unesterified DHA, the form that is taken up by the brain. Both kinetic parameters are independent of brain blood flow, thus they can represent brain DHA metabolism at rest or during changes in response to drugs, disease or physiological disturbance of blood flow. DHA incorporation is upregulated as a marker of new membrane synthesis in central visual regions following removal of an eye in the rat and with tumor growth in the brain. It is increased during neurotransmission following G-protein activation of synaptic cholinergic receptors, but unchanged in response to acute N-methyl-D-aspartate (NMDA) administration, which allows extracellular calcium into the cell, confirming that the signal is independent of extracellular calcium and likely mediated by calcium-independent phospholipase A2 (iPLA2). Studies in mice in which iPLA2-VIA (β) was knocked out confirmed this. The imaging method has been extended with positron emission tomography (PET) to show that human brain DHA consumption rate approximates 3.8mg/day, one fiftieth of the recommended daily DHA requirement.
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