Brain phospholipids

Each phospholipid class in a given tissue has a characteristic fatty acid composition. Though the same fatty acid may be present in a number of lipids, the quantitative fatty acid composition is different for each class of lipids and remains fairly constant during the growth and development of the brain. A typical distribution profile of the major fatty acids in rat brain phospholipids is given in Table 3.1. Not only do the phosphoglycerides differ in the structure of the polar head groups, or phospholipid... 

Linamurin is the principal cyanogenic glycoside in cassava its toxicity is due to hydrolysis by intestinal microflora releasing free cyanide (Padmaja and Panikkar 1989). Rabbits (Oryctolagus cuniculus) fed 1.43 mg linamurin/kg BW daily (10 mg/kg BW weekly) for 24 weeks showed effects similar to those of rabbits fed 0.3 mg KCN/kg BW weekly. Specihc effects produced by linamurin and KCN included elevated lactic acid in heart, brain, and liver reduced glycogen in liver and brain and marked depletion in brain phospholipids (Padmaja and Panikkar 1989). 

Recent interest has focused on the C20 5 eicosa-pentaenoic acid (EPA) and the C22 6 docosa-hexaenoic acids (DHA). These 3 (or n-3) polyunsaturated acids are formed from linolenic acid by marine algae and are found in fish oils.h The C22 5 and C22 6 acids can be converted to prostaglandins of the PG4 and PG5 series. DHA together with the 0)6 C22 4 acid constitutes over 30% of the fatty acids in brain phospholipids. In the... 

Rapoport S. I. (1999). In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling. Neurochem. Res. 24 1403-1415. 

Soderberg M., Edlund C., Kristensson K. and Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer s disease. Lipids 1991 26 421-425. 

Kitajka K, Puskas LG, Zvara A, Hackler L, Barcelo-Coblijn G, Yeo YK, Farkas T. The role of n-3 polyunsaturated fatty acids in brain Modulation of rat brain gene expression by dietary n-3 fatty acids. Proc. Natl. Acad. Sci U.S.A. 2002 99 2619-2624. Barcelo- Coblijn G, Hogyes E, Kitajka LG, Zvara A, Hackler L Jr, Nyakas C, Penke Z, Farkas T. Modification by docosahex-aenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids. Proc. Natl. Acad. Sci. U.S.A. 2003 100 11321-11326. 

Brain phospholipids. The brain is a rich source of phospholipids, and together with the spinal cord, it probably possesses the highest phospholipid content of any of the organs. There are many different types of phospholipids in the central nervous system. As they bypass the blood-brain barrier, adequate nutrition (biosynthesis) of the nerve cells is assured with these substances. Special... 

The composition of brain phospholipids has been extensively investigated by adsorption column- and thin-layer chromatography (TLC). Table 5 lists the major classes of brain phospholipids from different animal species, as compiled by Kuksis (16, 27-30). At the end of the 1990s, the fear of mad cow disease (BSE) may have addressed the purity criteria for the applications of brain phospholipids from cows. 

Syntheses and uses of isotopically labelled dienes and polyenes rapidly and selectively incorporated into brain phospholipids... 

Quantifying and Imaging Brain Phospholipid Metabolism In Vivo Using Radiolabeled Long Chain Fatty Acids... 

For these many reasons, it would be of interest to quantify and image in vivo FA kinetics in brain phospholipids, in animals and in humans. Our laboratory has elaborated a method and model to do this (Rapoport, In press Rapoport et al., 1997 Robinson et al., 1992). 

The complex representation of Fig. 1 can be simplified to Fig. 2, which identifies three compartments that have to be assessed experimentally to apply the FA model. These compartments are (1) plasma unesterified FA, (2) the precursor brain FA-CoA pool, and (3) the stable brain phospholipid compartment (Rapoport et al., 1997 Robinson et al., 1992). Fluxes between them—J, J2, J pa—defined in the legend to Fig. 2. The simplified Fig. 2 can be used because (1) the half-life of the FA tracer in plasma is less than 1 min, (2) FA uptake into brain from bloodis independent of cerebral blood flow over a wide range of unlabeled FA plasma concentrations (Chang et al., 1997a Yamazaki et al., 1994), (3) labeled FA in plasma rapidly equilibrates (1 min or less) with label in FA-CoA, the precursor pool for FA incorporation into brain phospholipids, and (4) the FA tracer in brain is rapidly incorporated into brain phospholipids (80-90% within 1 min) (Rapoport et al., 1997 Robinson et al., 1992). 

Rapid entry of a FA from plasma into the brain FA-CoA pool allows increased neuronal demand for the FA to be easily met by the large reservoir of unesterified FA in plasma. One to two minutes after a step elevation in plasma [9,10- H]palmitate or labeled arachidonate, specific activity of the respective brain FA-CoA pool has reached a steady state (Grange et al., 1995 Washizaki et al., 1994). At this time, the ratio of FA-CoA specific activity to plasma FA specific activity (X. in Eq. 4) is 0.02-0.04, attesting to marked dilution of plasma-derived FA-CoA by FA released from brain phospholipids (Fig. 2). 

We have derived and validated operational equations to quantify FA fluxes from plasma into the brain FA-CoA pool and from the FA-CoA pool into individual brain phospholipids, and turnover rates and half-lives within these phospholipids (Rapoport et al., 1997 Robinson et al., 1992). The incorporation rate of a FA radiotracer from plasma into a stable brain lipid compartment i is given by. 

Thus, the turnover rate (percent per unit time) of the unlabeled FA in brain phospholipid i, reflecting de-esterification followed by re-esterification, is given as... 

Distribution of Radiolabeled Fatty Acids Within sn- 1 and sn-2 Sites of Brain Phospholipids ... 

Estimated Acyl-CoA Dilution Coefficients X, and Half-Lives of Fatty Acids in Brain Phospholipids of Awake Rats... 

Selective Reduction by Chronic Lithium of Arachidonate Turnover in Rat Brain Phospholipids... 

Fig. 4. Cycling of arachidonate in a brain phospholipid following its release by receptor-initiated activation of PLA2. Following activation, unlabeled arachidonate is released from phospholipid (upper right) into the unesterified FA pool, which has been labeled by an intravenous injection of tracer. A fraction of the unesterified FA is converted to bioactive leukotrienes and eicosanoids. The remainder, with labeled and unlabeled FA taken up from blood into which label has been injected, is re-esterified into the brain arachidonoyl-CoA pool, from which it is incorporated into a lysophospholipid to reconstitute a labeled phospholipid at the site of PLA2 activation.

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