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T1 - Cholesterol synthesis in rat brain

Reduction of cholesterol synthesis in the mouse brain does ..

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In the mouse brain, cholesterol synthesis is high ..

Although amyloid plaque accumulation did not affect brain sterol orfatty acid synthesis rates in 24-hydroxylase WT or knockout mice, lossof one or both cholesterol 24-hydroxylase alleles increased longevity inAlzheimer's disease mice.

15/09/2014 · Cholesterol in brain disease: sometimes determinant and frequently ..

These studies suggest that reducing de novocholesterol synthesis in the brain will not substantially alter thecourse of Alzheimer's disease, but may confer a survival advantage.

LDL Cholesterol Changes Can Lower Brain Function | Time

Cholesterol synthesis in the brain

The reduced cholesterol flux through the brains of 24-hydroxylase KO mice also does not markedly affect the processing of APP to Aβ40 and Aβ42 peptides (see ). These in vivo results imply that levels of secretase activity are similar in WT/AD and KO/AD mice, and they suggest that intracellular cholesterol levels and distribution are normal in the KO mice. An extensive body of literature indicates that acute changes in intracellular cholesterol levels can alter the processing of APP in vitro (), in part by modifying membrane lipid composition, which in turn increases or decreases secretase activity (–). The difference between the in vivo results reported here and these in vitro results is possibly explained by the harsh pharmacological treatments used to change intracellular cholesterol levels, which can temporarily override the intricate regulatory mechanisms that normally maintain membrane cholesterol content within a narrow range (). In contrast, these regulatory mechanisms are intact in 24-hydroxylase KO mice based on the observation that brain cholesterol levels in the mutant mice are not different from those of WT mice (, ). Similarly, in vitro studies suggest that high concentrations of Aβ peptides can directly modulate cholesterol synthesis in cultured neurons and other cell types (), whereas here, no effect of extensive amyloid accumulation was observed on in vivo lipid synthesis (see ). These disparate findings may reflect differences in rates or extent of Aβ peptide accumulation.

In contrast to these findings, 24-hydroxylase KO mice exhibit an ≈50% decrease in de novo cholesterol synthesis and a corresponding 50% decrease in cholesterol excretion from the brain (, ), but these alterations do not affect rates of amyloid deposition, at least as judged by Congo Red staining (see ). This outcome is similar to that observed in ABCG1 transgenic and KO mice in which cholesterol synthesis rates are apparently decreased and increased, respectively, but neither of these changes affect APP levels or processing to amyloidogenic Aβ peptides (). Inasmuch as data from mice can be extrapolated to humans, these outcomes suggest that even if drugs such as statins were able to cross the blood–brain barrier and reduce cholesterol synthesis, they would not alter the deposition of amyloid in AD.

Cholesterol – Good for the brain, bad for the heart

15.09.2014 · Cholesterol in brain disease: sometimes determinant and frequently ..

N2 - While excess cholesterol may have deleterious consequences, as in the case of atherosclerosis, too little cholesterol may endanger the development of the brain. Different degrees of mental retardation are often observed in inborn errors of cholesterol synthesis, such as the Smith-Lemli-Opitz syndrome or in maternal phenylketonuria, where the metabolite of accumulating phenylalanine, phenylacetate, is an inhibitor of cholesterol synthesis. Lack of cholesterol during brain development as a consequence of these genetic defects leads to severe brain damage, microencephaly and mental retardation, which are also hallmarks of the fetal alcohol syndrome (FAS). The brain relies on the in situ synthesis of cholesterol, which occurs mostly in astrocytes. Astrocyte-produced cholesterol is utilized for cell proliferation, or is released, via astrocyte-secreted high density lipoprotein-like particles containing apolipoprotein E, outside the cell, where it is taken up and utilized by neurons for dendrite outgrowth and to form synapses. We propose the hypothesis that ethanol may disrupt cholesterol homeostasis during brain development, and that this effect may be responsible, at least in part, for the central nervous system dysfunctions observed in the FAS, which include altered astrocyte proliferation, neuronal death and diminished synaptic contacts.

AB - While excess cholesterol may have deleterious consequences, as in the case of atherosclerosis, too little cholesterol may endanger the development of the brain. Different degrees of mental retardation are often observed in inborn errors of cholesterol synthesis, such as the Smith-Lemli-Opitz syndrome or in maternal phenylketonuria, where the metabolite of accumulating phenylalanine, phenylacetate, is an inhibitor of cholesterol synthesis. Lack of cholesterol during brain development as a consequence of these genetic defects leads to severe brain damage, microencephaly and mental retardation, which are also hallmarks of the fetal alcohol syndrome (FAS). The brain relies on the in situ synthesis of cholesterol, which occurs mostly in astrocytes. Astrocyte-produced cholesterol is utilized for cell proliferation, or is released, via astrocyte-secreted high density lipoprotein-like particles containing apolipoprotein E, outside the cell, where it is taken up and utilized by neurons for dendrite outgrowth and to form synapses. We propose the hypothesis that ethanol may disrupt cholesterol homeostasis during brain development, and that this effect may be responsible, at least in part, for the central nervous system dysfunctions observed in the FAS, which include altered astrocyte proliferation, neuronal death and diminished synaptic contacts.

of circulating and brain cholesterol has ..
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  • Brain cholesterol synthesis is ..

    Brain Cholesterol Synthesis in Mice Is Affected by High Dose of Simvastatin but Not of Pravastatin.

  • >Cholesterol and the Brain | JustMEinT's General Blog

    Cholesterol synthesis in rat brain: Differential incorporation of mevalonolactone-2-C14 and potassium mevalonate-2-C14

  • Cholesterol: Synthesis, Metabolism, Regulation

    The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis

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Introduction to Cholesterol Metabolism ..

These studies were designed to characterize the regional differences in cholesterol concentration throughout the brain of the developing sheep and hamster, and to learn more about the origin of this cholesterol by measuring in vivo the rates of cholesterol synthesis and low density lipoprotein-cholesterol clearance by different regions of the central nervous system in these animal models. In both species whole brain cholesterol concentration increased several fold throughout fetal and early neonatal life. There were marked regional differences in cholesterol concentration throughout the brain, with the concentration being greatest in the areas richest in myelin. In both hamsters and sheep the differences in cholesterol concentration between the various regions correlated strongly with the differences in the rate of cholesterol synthesis. In no region of the central nervous system of the fetal and neonatal sheep could significant rates of LDL transport be detected. Together these studies show that cholesterol deposition in the rapidly developing central nervous system of the fetal and neonatal animal does not require the uptake of low density lipoprotein-cholesterol from the plasma, but instead appears to be critically dependent on the de novo synthesis of cholesterol within the brain itself.

The process of cholesterol synthesis can be ..

N2 - These studies were designed to characterize the regional differences in cholesterol concentration throughout the brain of the developing sheep and hamster, and to learn more about the origin of this cholesterol by measuring in vivo the rates of cholesterol synthesis and low density lipoprotein-cholesterol clearance by different regions of the central nervous system in these animal models. In both species whole brain cholesterol concentration increased several fold throughout fetal and early neonatal life. There were marked regional differences in cholesterol concentration throughout the brain, with the concentration being greatest in the areas richest in myelin. In both hamsters and sheep the differences in cholesterol concentration between the various regions correlated strongly with the differences in the rate of cholesterol synthesis. In no region of the central nervous system of the fetal and neonatal sheep could significant rates of LDL transport be detected. Together these studies show that cholesterol deposition in the rapidly developing central nervous system of the fetal and neonatal animal does not require the uptake of low density lipoprotein-cholesterol from the plasma, but instead appears to be critically dependent on the de novo synthesis of cholesterol within the brain itself.

Cholesterol in brain disease: sometimes determinant …

T1 - Disruption of cholesterol homeostasis in the developing brain as a potential mechanism contributing to the developmental neurotoxicity of ethanol

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