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Institutt for biomedisin

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BBB seminar: Michael A. Crawford

The unique role of the marine food chain in the evolution of the human brain with speculations on the reasons why docosahexaenoic acid has been exclusively used for vision and neural signalling over the 600 million years of multi-cellular evolution

Michael A. Crawford
Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, UK

Docosahexaenoic acid (C22:6ω3, DHA) is selectively found in signalling membranes for photoreception and neural systems which have evolved through 600 million years of multi-cellular evolution. Not only does molecular dynamics show that DHA bears a structural similarity to the retinoids involved as ligands for the conserved, mammalian retinoid X receptor (RXR) system, but cell-based assays show that DHA itself activates RXR. Recent studies show that this receptor system regulates the expression of some 107 neural genes. It is well known from depletion experiments that neural and visual function deteriorate without RXR, and DHA deficiency results in similar defects in rats and humans. Hence, we argue, DHA was an essential determinant of human cerebral expansion. Since the richest sources of DHA are marine organisms, human evolution most likely took place coastally and not inland as is popularly believed; there is recent fossil evidence to support this hypothesis.

What is so special about DHA? Why is it the only molecule used in the visual and neural membrane lipids? Why is there such exclusivity of the C22:6ω3 as opposed to its more readily made precursor: the ω3 docosapentaenoic acid (C22:5ω3)?

From present evidence it is difficult to find a compelling reason for the selectivity, which is usually considered to be a combination of mechanical properties, metabolic selectivity and protein/lipid interaction. However, we speculate on the possibility that it may have an as yet undescribed quantum function which would require the full six member sequence of methylene-interrupted double bonds and their π-electrons. Whereas neural signalling has been mainly described in terms of ion movements, this theory may fill in a gap as to parallel events concerning movement of electrons.

Professor Michael A. Crawford has been Director of the Institute of Brain Chemistry and Human Nutrition (IBCHN) at the London Metropolitan University since 1989. He started his investigations on the role of dietary polyunsaturated fatty acids in brain metabolism and function already in 1965 at the Nuffield Institute of Comparative Medicine in London, UK. Michael Crawford has done numerous dietary studies on populations in Africa, East Europe and the Mediterranean countries. At the IBCHN he has become particularly interested in the roles of dietary arachidonic and docosahexenoic acids in brain function in general and in non-transmittable diseases, now referred to as "The Metabolic Syndrome", including heart disease, diabetes and premature birth.