Cholesterol in brain

Fig. 4. Incorporation and persistence of Ci -cholesterol in brain, liver, and plasma. One-day-old chickens were injected with 4-Ci -cholesterol (Davison et al., 1958). (By courtesy of the Journal of Neurochemistry.)...

Cholesterol in Brain Membranes 315 13.8 Key Experiment Probes to Study ... 

It is interesting that H and C are incorporated from L-[methyl- H, C]-methionine into cholesterol and 5a-cholest-7-en-3P-ol in normal and tumorous rats. The exact mechanism of this incorporation is obscure at present. There has been an increased interest in the biosynthesis and metabolism of cholesterol in brain tissue. This area has also been reviewed recently. The primary pathway of sterol biosynthesis in adult rat brain seems to be via A -intermediates. It is interesting that the conversion of squalene into sterols by microsomal fractions from brains of immature rats requires the lOOCKX) X g supernatant fraction from liver, the corresponding supernatant fraction from brain being inactive. ... 

CYP7A1 catalyzes the 7a-hydroxylation of cholesterol, the first and rate limiting step of bile acid synthesis. This is also the principal way to eliminate cholesterol. CYP7B1 is primarily expressed in brain and catalyzes the synthesis of various neurosteroids and also the 7a-hydroxylation of oxysterols. 

Haider SS, Hasan M, Islam F. 1980. Effect of air pollutant hydrogen sulfide on the levels of total lipids, phospholipids cholesterol in different regions of the guinea pig brain. Indian J Exp Biol 18 418-420. 

Koldamova, RP, Lefterov, IM, Ikonomovic, MD, Skoko, J, Lefterov, PI, Isanski, BA, DeKosky, ST, and Lazo, JS, 2003. 22R-hydroxycholesterol and 9-cw-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid beta secretion. J Biol Chem 278, 13244-13256. 

This assay has been used by some authors to evaluate the in vitro effects of antioxidant extracts on LDL oxidation (Viana and others 1996 Cirico and Omaye 2006 Kedage and others 2007 Vayalil 2002 Garcfa-Alonso and others 2004 Tarwadi and Agte 2005). Oboh and others (2007) confirmed that hot pepper prevents in vitro lipid peroxidation in brain tissues. Indeed, Bub and others (2000) demonstrated that a moderate intervention with vegetable products rich in carotenoids reduces lipid peroxidation in men. Nicolle and others (2003) evaluated the effect of carrot intake on antioxidant status in cholesterol-fed rats. Later on, they showed that lettuce consumption improves cholesterol metabolism and antioxidant status in rats (Nicole and others 2004). 

The most abundant of these in brain is cholesterol. Unlike other tissues, normal adult brain contains virtually... 

Cutler, R. G., Kelly, J., Storie, K. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer s disease. Proc. Natl Acad. Sci. U.S.A. 101 2070-2075,2004. 

Sterols are compounds that have a steroid structure (Figure 12.5) and contain a hydroxyl group, which is capable of forming an ester. They are widespread in nature and commonly exist as mixtures of the free sterol and esters with fatty acids. Cholesterol (Figure 12.5) is by far the commonest sterol in animals, a high concentration being found in brain, nervous tissue and membranes. Plants... 

Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, et al. 2001. On the turnover of brain cholesterol in patients with Alzheimer s disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 314 45-48. 

Researchers have reasoned that if the water-soluble peptide leu-enkephalin could be conjugated with an oxidizable hydrophobic chain, and further shielded with a hydrophobic domain provided by cholesterol via an ester linkage, the modihed leu-enkephalin could become sufficiently hydrophobic to breach the blood-brain barrier. The oxidation of one of the engineered domains in the brain would produce an ionic form that cannot redistribute back into blood, and is essentially locked in. The ester linkages could then be hydrolyzed by esterases in brain tissues to release biologically active leu-enkephalin (Figure 13.12). 

Aside from its murky role in brain function, alpha-linolenic acid has some well-documented effects on heart disease. It reduces the risk of blood-clot formation, lowers the chance of potentially lethal irregular heartbeat, and probably has an antiinflammatory effect on blood vessels. Several studies have found a link between increased intake of the acid and reduced risk of death from heart disease. Alpha-linolenic acid helps lower blood cholesterol, but flaxseed has another component that performs this function even more effectively. This is soluble fiber, which isn t absorbed by the body and passes right through the digestive system. On its journey through the digestive tract, the fiber binds cholesterol and prevents it from... 

Cholesterol is both absorbed from the intestinal tract and synthesized from acetate via squalene, principally in the liver. The quantities produced are substantial. Daily biosynthesis is 600 mg, and dietary uptake may supply another 300 mg.182 Not only is there a large amount of cholesterol in the brain and... 

Fig. 6.7 Filipin staining for free cholesterol in field CA3 of the hippocampus. A section from a normal rat, showing light staining for free cholesterol in pyramidal neurons (arrows). B section from a rat that had been injected with kainate 1 day earlier, showing intense filipin staining in affected hippocampal neurons (arrows). Scale = 250 // m. Reproduced with kind permission from Ong et al., 2003, Brain Pathology 13 250-262. Blackwell Publishing...

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