Brain cholesterol metabolism

C. Brain Cholesterol Metabolism (Long-Term Experiments ). 184... 

Histochemical, cytochemical, developmental, and biochemical studies indicate that much of the brain cholesterol is localized in the lipid-protein layers of the myelin sheath. As a result, this cholesterol is largely removed from the normal metabolic environment of the brain. Thus, although nervous tissue contains relatively large amounts of lipid, biosynthesis and the mean turnover rate of the typical myelin lipids including cholesterol are quite slow. Nevertheless dynamic metabolism may be found in small pools of, for example, cell or organelle membrane, cytoplasmic lipid, or outer parts of the myelin sheath. Such possibilities may serve to explain some of the various anomalous results reported by many workers studying brain cholesterol metabolism. 

Kolsch H, Lutjohann D, lessen F, Popp J, Hentschel F, Kelemen R Schmitz S, Maier W, Heun R (2009) CYP46A1 variants influence Alzheimer s disease risk and brain cholesterol metabolism. Eur Psy- 2718. 

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). 

Dietschy, J. M. and Turley, S. D. Thematic review series brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. /. Lipid Res. 45 1375-1397,2004. 

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. 

Pharmaceuticals. Lecithin and especially purified phosphatidylcholine can act as excipients in pharmaceutical (drug) formulation to enhance and control the Unavailability of the active component. Moreover, phosphatidylcholine can be utilized as a diedelic source, as it involved in the cholesterol metabolism and the metabolism of fats in the liver also, it can be utilized as a precursor of brain acetylcholine, as neurotransmiticr. 

Manganese Skeletal deformities Gonadal and reproductive dysfunction Defective cholesterol metabolism Brain abnormalities Respiratory illness Ataxia Motor neuron diseases... 

The brain is one of the most cholesterol rich organs of the body and contains 25% of total body cholesterol [92]. While the body manages cholesterol metabolism primarily through the liver, the brain cholesterol compartment is essentially isolated from body cholesterol pools by the blood brain barrier (BBB). During early CNS development, the rate of cholesterol synthesis is quite high due to extensive myelination. As the brain matures, cholesterol synthesis and turnover slow dramatically with an estimated total turnover rate ranging from 4-6 months [93] in adult rat brain. The turnover rate is even slower in humans than in rodents (0.03% per day vs. 0.4% in rodent) [94]. 

Neurons rely upon a ready supply of cholesterol for maintaining a broad array of physiological functions such as membrane synthesis, myeUn maintenance, electrical signal transduction, synaptic transmission, and plasticity. Cholesterol metabolism in the CNS is unique compared with the rest of the body. Because of the existence of the blood-brain barrier (BBB), almost all the sterol required for new membranes comes from de novo synthesis within the CNS [33]. In addition, the brain has evolved highly efficient mechanisms to maximize the utihzation of cholesterol. UnUke other membrane lipid components, cholesterol cannot be synthesized at neuronal terminals. Therefore, synaptic function depends largely on cholesterol supplied from either axonal transport from the cell body and or uptake of Upidated ApoE produced by astroglia via neuronal lipoprotein receptors. 

Research into the healtli benefits of the PMFs has been extensive two recent reviews are given in references (3) and (4). PMF effects on cancerous tumor growtli/prevention (4), cholesterol metabolism (3), and inflammation (4) have been stuped in the most detail. Recent studies have also looked at the effect on insulin resistance (5) and treatment of brain disorders (6). 

The second line of evidence suggesting metabolic stability of brain cholesterol was published shortly after the classical experiments of Waelsch et al. (1940). Bloch et al. (1943) fed cholesterol labeled with deuterium to an adult dog for 3 days although at the end of 6 days the marked material could be recovered from the other organs examined, none was found in the brain or spinal cord. Bloch and his colleagues concluded that their observations illustrated the lack or paucity of metabolic interchange between the sterol of the central nervous system and that of the blood. If 4-C -cholesterol is injected into newly bom animals... 

It seems that a large proportion of adult rat, rabbit, or chicken brain cholesterol undergoes very slow metabolism. Since about 70% of brain cholesterol is located in the myelin sheath, it is probable that at least part of this structure is metabolically a relatively stable tissue component. Other studies on brain lipids support this view. Thus distribution of rat brain cerebroside sulfate is similar to that of cholesterol and turnover of sulfatide is also exceedingly slow. Furthermore, Davison and Gregson (1962) found that persisting radioactivity was associated primarily with the myelin fraction prepared from brains of rats previously injected with S -sulfate or methionine. 

Not all brain cholesterol is, however, metabolically stable, for some turnover has been demonstrated in the gray matter of young rabbits (Davison et al, 1959a). Other experiments by Kabara and Okita (1961) also indicate that there are several sterol compartments in brain, each with a difiEerent turnover rate. Very rapid labeling of a small cholesterol pool followed injection of or H -labeled precursors into young adult mice at a rate equivalent to almost complete turnover in 80 minutes. Pritchard (1963) also found catabolism of 50% of C -Iabeled cerebral cholesterol 30 days after injection of 1-C -acetate into 1-day-old rats, although during the remainder of the experimental period (40 days) the radioactive cholesterol was retained in the brain with little loss. 

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