The nervous system has an absolute molecular species requirement for proper function

Abstract

A considerable body of biological evidence has accumulated that suggests that docosahexaenoic acid (22:6n3) is an essential component in the nervous system. Moreover, it appears from these studies that long chain polyunsaturates of the n-6 family such as arachidonate (20:4n6) and docosapentaenoate (22:5n6) cannot substitute for 22:6n3. This evidence is briefly reviewed and two hypotheses centering upon either biochemical or biophysical aspects of polyunsaturate function are presented and discussed. It is concluded that a bioactive metabolite of 22:6n3 is not responsible for its function in brain and that the best hypothesis asserts that a membrane function of a 22:6n3-containing species of phospholipid, such as phosphatidylserine, is critical for optimal neural function. Moreover, data are presented indicating that the biophysical properties of various highly unsaturated species of phospholipid are distinguishable. It is further contended that these species are not randomly distributed in membranes and thus the differences in physical properties may be amplified. It is concluded that a conceptual framework is needed in which the distinct membrane roles of phospholipid species may be understood as a function of the positions and numbers of double bonds. Only then may the critical role of the highly unsaturated n-3 polyunsaturates in the brain and retina be understood.

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

“…Various fatty acids serve different roles in the nervous system and in the body and it has been suggested that the nervous system has an absolute molecular species requirement for proper function [106]. Studies in our laboratory offer a confirmation for this suggestion and provide an added qualifying requirement, viz.…”

“…For example, Bourre [14] claimed that alpha-linolenic acid controls the composition of nerve membranes, which implies an inverse relationship between alpha-linolenic acid and cholesterol level. Salem and Niebylski [106] proposed that DHA or (22:6, n-3) controls the level of cholesterol as well as the composition and function of the neuronal membrane. We recently reviewed a number of studies that provided support for reducing neuronal membrane cholesterol by dietary supplementation of an n-3/n-6 compound in a ratio of 1:4 [125].…”

Mechanisms of action of docosahexaenoic acid in the nervous system

“…The failure of this initial hypothesis led to proposals that are based on the concept that the active form of DHA is in the form of a phospholipid (102)(103)(104). Little progress was made on this intractable problem until workers focused on this hypothesis.…”

Essential fatty acids and the brain: possible health implications

“…This important ®nding raised many questions, but in particular the issue about the biochemical and biophysical mechanisms that lead to their essentiality. To date, a multitude of mechanisms have been explored, for example, their eects on; the structural integrity and¯uidity of membranes [33,130]; enzyme activities [80,120,125]; lipid-protein interactions [117]; and their role as precursors for eicosanoids, such as prostaglandins, leukotrienes and thromboxanes.…”