Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

Koper, Jan W.; Zeinstra, E.; Lopes‐Cardozo, M.; Golde, L.M.G. Van

doi:10.1016/0005-2760(84)90233-9

Cited by 29 publications

(21 citation statements)

References 24 publications

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“…Addition of BSA alone (not shown) or of octanoate had no effect on either fatty acid, cholesterol, or sulphatide synthesis. In contrast, both palmitate and oleate reduced the synthesis, not only of fatty acids and sterols, but also of sulphatides, which are synthesized only by oligodendrocytes (Koper et al, 198413;Singh and Pfeiffer, 1985).…”

Section: Effect Of Various Fatty Acids On Lipid Synthesis By Glial Cumentioning

confidence: 90%

Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Sykes

Lopes‐Cardozo

1990

Glia

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Glial cells were isolated from the cerebra of 7-day-old rats and maintained in culture in a chemically defined medium that favours the development of oligodendrocytes. Acetate, butyrate, or albumin-bound hexanoate, octanoate, decanoate, laurate, myristate, palmitate, oleate, linoleate, or arachidonate was added to the culture medium. The incorporation of [3H]acetate into fatty acids and cholesterol and [35S]sulphate into sulphatide, and the activities of the oligodendrocyte marker enzymes 2',3'-cyclic-nucleotide 3'-phosphodiesterase and glycerol 3-phosphate dehydrogenase were measured. The composition of the glial cell population (the number of astrocytes and oligodendrocytes) in these cultures was studied by immunocytochemistry. Results show that 1) long-chain fatty acids depress the synthesis of fatty acids, cholesterol, and sulphatide; and 2) the presence of long-chain, in contrast to short-chain, fatty acids in the culture medium lowers the activities of 2',3'-cyclic-nucleotide 3'-phosphodiesterase and glycerol 3-phosphate dehydrogenase and decreases the number of oligodendrocytes. Our results suggest that long-chain fatty acids exert a negative influence on the development of oligodendrocytes in the culture system used.

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Section: Effect Of Various Fatty Acids On Lipid Synthesis By Glial Cumentioning

confidence: 90%

Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Sykes

Lopes‐Cardozo

1990

Glia

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“…22 Because most studies on neuronal cells have been made on embryonal cells, there is a possibility that older neurons may lose their capacity to synthesize cholesterol. 23 Pfrieger has recently discussed the possibility that neurons may switch from cholesterol production during embryonic stage to "outsourcing" after birth. He points out that synthesis of the sterol molecule requires a diverse array of enzymes that are distributed in different subcellular organelles and consumes large amounts of energy.…”

Section: Mechanism and Site Of Synthesis Of Brain Cholesterolmentioning

confidence: 99%

Brain Cholesterol: Long Secret Life Behind a Barrier

Björkhem

Meaney

2004

ATVB

894

732

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Abstract-Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier efficiently protecting it from exchange with lipoprotein cholesterol in the circulation. Thus, there is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Under steady-state conditions, most of the de novo synthesis of cholesterol in the brain appears to be balanced by excretion of the cytochrome P-450 -generated oxysterol 24S-hydroxycholesterol. This oxysterol is capable of escaping the recycling mechanism and traversing the blood-brain barrier. Cholesterol levels and cholesterol turnover are affected in neurodegenerating disorders, and the capacity for cholesterol transport and recycling in the brain seems to be of importance for the development of such diseases. The possibility has been discussed that administration of inhibitors of cholesterol synthesis may reduce the prevalence of Alzheimer disease. No firm conclusions can, however, be drawn from the studies presented thus far.In the present review, the most recent advances in our understanding of cholesterol turnover in the brain is discussed. Key Words: brain cholesterol Ⅲ blood-brain barrier Ⅲ cholesterol 24S-hydroxylase Ⅲ Alzheimer disease Ⅲ statins H ighly sophisticated regulatory systems have evolved for the maintenance of cholesterol homeostasis in the body. There is a distinct difference between the situation in the central nervous system and that in most other extrahepatic tissues. Outside the brain, the cellular needs for cholesterol is covered by de novo synthesis and by cellular uptake of lipoprotein cholesterol from the circulation. In the brain, the blood-brain barrier effectively prevents uptake from the circulation, and de novo synthesis is responsible for practically all cholesterol present in this organ. The independence of the isolated pool of cholesterol in the brain is likely to reflect a high need for constancy in the cholesterol content of membrane and myelin, a constancy that would be difficult to keep if brain cholesterol had been exchangeable with lipoprotein cholesterol.The importance of cholesterol in the nervous system was recognized as early as 1834, when Couerbe's observations lead him to regard cholesterol as un element principal of the nervous system. 1 Despite concerted efforts in the interim, it is only during the past few decades that the brain has begun to surrender the secrets of the behavior of one of its most abundant lipids.In the present brief review, we summarize the basal characteristics of brain cholesterol and some recent findings with respect to homeostasis of this compound in the brain. Emphasis is put on the newly described relation betwee...

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“…Proposals have been made that these lipids are essential for the assembly and com paction of the myelin sheath [23], We pro pose that the defect in the quaking mutant in respect to myelination is a synthetic abnor mality localized in the oligodendrocytes, the myelin-forming cell [8], which provokesadefective myelin assembly at a very early stage.…”

Section: Discussionmentioning

confidence: 99%

“…19], Morphologically, oligodendrocytes in quaking mice appear to he normal in size and in the time of appear ance but increased in numbers (15). It lias been shown that glucose is a substrate for lipid synthesis by rat brain oligodendrocytes [23]. In the rat.…”

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confidence: 99%

Incorporation of Radioactivity from U-<sup>14</sup>C-GIucose into Oligodendrocytes and Myelin of Quaking Mice and Their Littermate Controls

Chao¹,

Bourre²

1986

Dev Neurosci

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Oligodendrocytes and myelin were purified from the cerebra of quaking mice and their littermate controls (11–60 days of age) after injecting the animals intraperitoneally with U-¹⁴C-glucose. A peak of incorporation of radioactivity in the lipid extract of oligodendrocytes of both quaking and normal mice at 16–18 days of age was found, suggesting that the onset of myelination in the cerebra starts approximately at the same time for quaking mice and their littermate controls. Nevertheless the level of incorporation per cell was lower in the oligodendrocytes of quaking mice (50% of the control). The pattern of incorporation into myelin during development was similar between the two strains, but the specific activity as measured in dpm/mg protein was higher in the myelin of young quaking animals (up to16 days). Peaks of incorporation were found in cerebrosides and sulfatides of oligodendrocytes and myelin in normal controls at 18 days. In the quaking mice these peaks were absent in oligodendrocytes and much delayed in the myelin of the mutant. The results would suggest that the defect in the quaking mutant in respect to myelination is in oligodendrocyte metabolism and thus in an early stage of the assembly of the myelin membrane.

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Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

Cited by 29 publications

References 24 publications

Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Effect of exogenous fatty acids on lipid synthesis, marker‐enzymes, and development of glial cells maintained in serum‐free culture

Brain Cholesterol: Long Secret Life Behind a Barrier

Incorporation of Radioactivity from U-<sup>14</sup>C-GIucose into Oligodendrocytes and Myelin of Quaking Mice and Their Littermate Controls

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