Biochemical maturation of the central nervous system

Dalal, K.; Einstein, Elizabeth Roboz

doi:10.1016/0006-8993(69)90237-6

Cited by 78 publications

(14 citation statements)

References 28 publications

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“…Immature myelin is characterized by a high level of phospholipids and low level of cholesterol and cerebrosides [6,8], At birth we found that about 6.2% of the dry weight of the cerebrum was cholesterol and 0.37% were cere brosides. This relatively high percentage of cholesterol at birth is in contrast with the value given by D alal and Roboz Einstein [6] who found only 0.5% cholesterol per dry weight of whole brain.…”

Section: Whole Brain Studymentioning

confidence: 99%

“…Cholesterol and cerebroside concentrations have been recognized in the literature as an index of myelination [6,8], cholesterol because of its high concentration in myelin (70% of total brain cholesterol in the adult rat [7]) and cerebrosides because of their high myelin specificity [8]. In the rabbit, myelination of the cerebrum seems to be near completion at about 90 days of age when the values for cholesterol and cerebroside concentration approxi mate the adult levels ( fig.…”

Section: Whole Brain Studymentioning

confidence: 99%

“…This aspect has not been as extensively investigated in the rabbit, which is a useful and a widely stud ied laboratory animal, although some studies on CNS water content [17] and lipid and protein changes during maturation have been reported for the rab bit [6,25].…”

Section: Introductionmentioning

confidence: 99%

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Growth and Development of the Rabbit Brain

et al. 1972

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Section: Whole Brain Studymentioning

confidence: 99%

Section: Whole Brain Studymentioning

confidence: 99%

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Growth and Development of the Rabbit Brain

et al. 1972

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“…1-4 the sections were prepared from 9-day-old rabbits, which are actively engaged in myelination (16). We also studied the LDL receptor in sections from adult rabbit brain and obtained the same general results.…”

Section: Resultsmentioning

confidence: 99%

“…Briefly, sections were treated with proteinase K (10 ,ug/ml, 37TC, 30 min) in adult tissues or Triton X-100 in neonatal tissues, acetylated, and dehydrated. After thorough drying, 70 ,ul of hybridization mixture containing 3"S-labeled probe (107 cpm/ml, with 10 mM dithiothreitol) was spotted on each slide, sealed under a cover glass, and incubated at 550C for 16 hr. Slides were then rinsed, digested with ribonuclease A (20 ug/ml, 37°C, 30 min), washed in 15 mM sodium chloride/1.5 mM sodium citrate at pH 7 for 30 min at 55°C, and dried.…”

Section: Methodsmentioning

confidence: 99%

Localization of mRNA for low density lipoprotein receptor and a cholesterol synthetic enzyme in rabbit nervous system by in situ hybridization.

Swanson

Simmons

Hofmann

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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The low density lipoprotein receptor and one of its ligands, apoprotein E, are known to be synthesized in the central nervous system. In the current study, we used in situ hybridization to localize the receptor mRNA in selected neurons and glia throughout the nervous system of 9-day-old rabbits. Particularly high levels were found in sensory ganglia, sensory nuclei, and motor-related nuclei. The same regions contained high levels of mRNA for 3-hydroxy-3-methylglutaryl-coenzyme A synthase, a regulated enzyme in cholesterol biosynthesis. The distribution of low density lipoprotein receptor mRNA was similar in mature and immature rabbits. The data suggest that certain cells in the nervous system have high requirements for cholesterol, which they satisfy through cholesterol synthesis and through receptor-mediated uptake of cholesterol-carrying lipoproteins. The latter originate in astrocytes which synthesize and secrete apoprotein E. These data suggest that the nervous system of mammals contains an active system for continuous redistribution and recycling of cholesterol that is physically distinct from the lipoprotein transport system in plasma.The low density lipoprotein (LDL) receptor binds cholesterol-carrying plasma lipoproteins that contain apoprotein (apo) B-100 or apoE. Binding leads to cell uptake by receptormediated endocytosis, thereby supplying cholesterol to cells (1). The production of LDL receptors is driven by a cell's cholesterol requirement. Cells that require large amounts of cholesterol, such as those in the liver and adrenal gland and those that grow in tissue culture, produce relatively large numbers of LDL receptors. Cells with low requirements, such as resting lymphocytes, produce few receptors. When the LDL receptor is genetically defective, as in patients with familial hypercholesterolemia or in Watanabe heritablehyperlipidemic (WHHL) rabbits, LDL is not taken up by cells normally, and plasma LDL levels rise (2).One of the ligands for the LDL receptor, apoB-100, is secreted almost exclusively by the liver (3). The other ligand, apoE, is secreted by hepatic and extrahepatic cells. One nonhepatic cell type shown to secrete apoE is the peritoneal macrophage (4). When loaded with excess cholesterol, macrophages secrete cholesterol-containing lipoproteins that contain apoE, which targets the lipoproteins to LDL receptors. ApoE-containing lipoproteins are also secreted by macrophages that enter damaged peripheral nerves and become engorged with cholesterol derived from degraded myelin (5,6). When the nerve regenerates, the neurons and Schwann cells produce LDL receptors and this allows them to use the lipoprotein-bound cholesterol secreted from the macrophages. Thus, apoE and the LDL receptor play a role in the healing of peripheral nerves.A role for apoE in the central nervous system (CNS) was demonstrated by Boyles et al. (5), who showed by immunocytochemistry that astrocytes produce apoE. This finding stimulated a search for LDL receptors in the brain. Hofmann et al. (7), using RNA blot...

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