Lipid rafts, cholesterol, and the brain

Korade, Željka; Kenworthy, Anne K.

doi:10.1016/j.neuropharm.2008.02.019

Cited by 276 publications

(216 citation statements)

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“…The increased synthesis of cholesterol as a mechanism to maintain homeostasis has, in fact, precedence in the study of alkylphospholipids which, as proposed for PMA, interact with, and consequently, disrupt membranes. 31 Another compelling observation in our study is the significant decrease in several interrelated metabolites associated with neuronal function and development. Among these, there is a decrease in Lac concurrent with observed increases in Glc.…”

Section: Discussionmentioning

confidence: 64%

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

et al. 2016

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Techniques based on nuclear magnetic resonance (NMR) for imaging and chemical analyses of in vivo, or otherwise intact, biological systems are rapidly emerging and finding diverse applications within a wide range of fields. Very recently, several NMR-based techniques have been developed for the zebrafish as a model animal system. In the current study, the novel application of high-resolution magic angle spinning (HR-MAS) NMR is presented as a means of metabolic profiling of intact zebrafish embryos. Toward investigating the utility of HR-MAS NMR as a toxicological tool, these studies specifically examined metabolic changes of embryos exposed to polymethoxy-1-alkenes (PMAs)-a recently identified family of teratogenic compounds from freshwater algae-as emerging environmental contaminants. One-dimensional and two-dimensional HR-MAS NMR analyses were able to effectively identify and quantify diverse metabolites in early-stage (£36 h postfertilization) embryos. Subsequent comparison of the metabolic profiles between PMA-exposed and control embryos identified several statistically significant metabolic changes associated with subacute exposure to the teratogen, including (1) elevated inositol as a recognized component of signaling pathways involved in embryo development; (2) increases in several metabolites, including inositol, phosphoryl choline, fatty acids, and cholesterol, which are associated with lipid composition of cell membranes; (3) concomitant increase in glucose and decrease in lactate; and (4) decreases in several biochemically related metabolites associated with central nervous system development and function, including c-aminobutyric acid, glycine, glutamate, and glutamine. A potentially unifying model/hypothesis of PMA teratogenicity based on the data is presented. These findings, taken together, demonstrate that HR-MAS NMR is a promising tool for metabolic profiling in the zebrafish embryo, including toxicological applications.

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Section: Discussionmentioning

confidence: 64%

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

et al. 2016

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“…MLRs have been implicated in various physiological cellular processes, such as protein membrane trafficking and signal transduction, and they have been demonstrated to play roles in synaptic plasticity and contribute to neuropathologies, such as Alzheimer's disease, Parkinson's disease, and Huntington disease (Hanzal-Bayer, Hancock, 2007;Karasinska, Hayden, 2011;Korade, Kenworthy, 2008;Sebastião et al, 2013;Simons, Toomre, 2000). Cholesterol is a key component of MLRs, as its depletion disrupts MLRs and leads to synaptic dysfunction or loss of synapses (Fielding, Fielding, 2003;Korade, Kenworthy, 2008;Sebastião et al, 2013). Cholesterol is responsible for MLRs maintenance in a liquid-ordered phase (Marwali et al, 2003).…”

Section: The Concept Of Mlrs/nmda Receptorsmentioning

confidence: 99%

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

Cruz

Magro

Lima

et al. 2017

Braz. J. Pharm. Sci.

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Membrane/lipid rafts (MLRs) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (statins) can disable the N-methyl-D-aspartate (NMDA) receptor through disruption of MLRs and, in turn, decrease NMDA-mediated anxiety. This hypothesis will contribute to understanding the critical roles of simvastatin in treating anxiety via the NMDA receptor.Uniterms: Anxiolytic effects. Membrane/lipid rafts. N-methyl-D-aspartate. Simvastatin.

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“…Cholesterol is the major structural component of cellular membranes and myelin. It is also a precursor of oxysterols, steroid hormones, and bile acids [2] .…”

Section: Major Lipid Classes and Functions In The Brainmentioning

confidence: 99%

“…These lipids consist of glycerophospholipids (GPs), sphingolipids, and cholesterol in roughly equimolar proportions [1] . The brain contains about 20% of the total body cholesterol [2] . Cholesterol is primarily derived from local synthesis, whereas uptake of lipoprotein particle-derived cholesterol from the peripheral circulation is usually prevented by the blood-brain-barrier.…”

mentioning

confidence: 99%

Lipid metabolism in Alzheimer’s disease

Liu

Zhang

2014

Neurosci. Bull.

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Lipids play crucial roles in cell signaling and various physiological processes, especially in the brain. Impaired lipid metabolism in the brain has been implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), and other central nervous system insults. The brain contains thousands of lipid species, but the complex lipid compositional diversity and the function of each of lipid species are currently poorly understood. This review integrates current knowledge about major lipid changes with the molecular mechanisms that underlie AD pathogenesis. Keywords: brain aging; lipid metabolism; Alzheimer's disease ·Review· IntroductionLipids are abundant in the brain. These lipids consist of glycerophospholipids (GPs), sphingolipids, and cholesterol in roughly equimolar proportions [1] . The brain contains about 20% of the total body cholesterol [2] . Cholesterol is primarily derived from local synthesis, whereas uptake of lipoprotein particle-derived cholesterol from the peripheral circulation is usually prevented by the blood-brain-barrier. Lipids, especially cholesterol, have recently been extensively studied in many neurodegenerative diseases. Impairment of cholesterol metabolism (synthesis, transport, and utilization by neurons) in the brain is linked to Alzheimer's disease (AD) and the aging process. In addition, lipid oxidation products accumulate at high levels in aging tissues in mice [3] . Recent studies have demonstrated the important role of altered metabolism in AD [4] . Sphingomyelinases promote apoptosis in human primary neurons through the generation of a proapoptotic molecule, ceramide [5] .Moreover, upregulated arachidonic acid metabolism has been reported in hAPP-J20 AD mice as well as in the AD brain, particularly in regions having high densities of senile plaques with activated microglia [6,7] . Although the potential link between cholesterol and AD pathogenesis has been intensively studied, growing evidence suggests that other lipids, such as sphingolipids and GPs, also play an important role. Here, we review some recent advances in understanding the role lipids play in the aging process and AD pathogenesis. Major Lipid Classes and Functions in the BrainAlthough most lipids serve as structural lipids in cell membranes, they are also directly involved in membrane trafficking, intracellular architecture, and the regulation of proteins and sub-compartments in membranes (lipid rafts) (Table 1). Eukaryotic organisms might contain a dozen major lipid classes, each comprising hundreds of individual molecular species [8] . Lipids have the potential to generate 9 000-100 000 molecular species [9,10] , and a mammalian cell may contain 1 000-2 000 [11] . The brain is one of the most lipid-enriched organs, containing several major classes, such as cholesterol, GPs, sphingolipids and fatty acids [12] . The biological significance of the compositional complexity of lipids is poorly understood. However, the recent development of the shot-gun lipidomics technique may provide more sensitive and quant...

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Lipid rafts, cholesterol, and the brain

Cited by 276 publications

References 144 publications

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

Lipid metabolism in Alzheimer’s disease

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