scholarly journals Cholestenoic Acid Is an Important Elimination Product of Cholesterol in the Retina: Comparison of Retinal Cholesterol Metabolism with That in the Brain

2011 ◽  
Vol 52 (1) ◽  
pp. 594 ◽  
Author(s):  
Natalia Mast ◽  
Rachel Reem ◽  
Ilya Bederman ◽  
Suber Huang ◽  
Pier Luigi DiPatre ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Cholestenoic Acid ◽  
The Brain

scholarly journals Resilience, plasticity and robustness in gene expression during aging in the brain of outbred deer mice

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
E Soltanmohammadi ◽  
Y Zhang ◽  
I Chatzistamou ◽  
H. Kiaris
Keyword(s):  
Gene Expression ◽  
Cholesterol Metabolism ◽  
Expression Profiles ◽  
Deer Mice ◽  
Abrupt Changes ◽  
Transcriptional Changes ◽  
Thrombospondin 4 ◽  
Whole Transcriptome ◽  
The Brain ◽  
Shed Light

Abstract Background Genes that belong to the same network are frequently co-expressed, but collectively, how the coordination of the whole transcriptome is perturbed during aging remains unclear. To explore this, we calculated the correlation of each gene in the transcriptome with every other, in the brain of young and older outbred deer mice (P. leucopus and P. maniculatus). Results In about 25 % of the genes, coordination was inversed during aging. Gene Ontology analysis in both species, for the genes that exhibited inverse transcriptomic coordination during aging pointed to alterations in the perception of smell, a known impairment occurring during aging. In P. leucopus, alterations in genes related to cholesterol metabolism were also identified. Among the genes that exhibited the most pronounced inversion in their coordination profiles during aging was THBS4, that encodes for thrombospondin-4, a protein that was recently identified as rejuvenation factor in mice. Relatively to its breadth, abolishment of coordination was more prominent in the long-living P. leucopus than in P. maniculatus but in the latter, the intensity of de-coordination was higher. Conclusions There sults suggest that aging is associated with more stringent retention of expression profiles for some genes and more abrupt changes in others, while more subtle but widespread changes in gene expression appear protective. Our findings shed light in the mode of the transcriptional changes occurring in the brain during aging and suggest that strategies aiming to broader but more modest changes in gene expression may be preferrable to correct aging-associated deregulation in gene expression.

scholarly journals Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Brain ◽  
Brain Function ◽  
Mass Spectrometry Imaging ◽  
Cholesterol Metabolism ◽  
Biologically Active ◽  
Wild Type ◽  
Tissue Slices ◽  
The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

scholarly journals 27-Hydroxycholesterol Promotes the Transfer of Astrocyte-Derived Cholesterol to Neurons in Co-cultured SH-SY5Y Cells and C6 Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Yushan Wang ◽  
Xiaona Zhang ◽  
Tao Wang ◽  
Wen Liu ◽  
Lijing Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholesterol Metabolism ◽  
Feedback Mechanism ◽  
Cholesterol Homeostasis ◽  
Membrane Cholesterol ◽  
C6 Cells ◽  
Cholesterol Accumulation ◽  
Cholesterol Levels ◽  
Related Proteins ◽  
The Brain

Abnormality in cholesterol homeostasis in the brain is a feature of Alzheimer’s disease (AD). 27-Hydroxycholesterol (27-OHC) has been identified as a possible biomarker of AD, but its effects on cholesterol metabolism have not been fully characterized. This study was aimed to investigate the impacts of 27-OHC on cholesterol metabolism in nerve cells. SH-SY5Y cells and C6 cells were co-cultured and treated with 5, 10, and 20 μM 27-OHC for 24 h. Results showed that 27-OHC decreased cholesterol levels and up-regulated the expression of transport-related proteins in C6 cells. In SH-SY5Y cells, 27-OHC increased cholesterol accumulation, especially on plasma membrane (PM), which was consistent with the up-regulation of expressions of cholesterol endocytosis receptors, lipid raft-related proteins, and cholesterol esterase. Simultaneously, accumulation of membrane cholesterol promoted cholesterol conversion to 24S-OHC by CYP46A1(24S-hydroxylase) transfer from the endoplasmic reticulum (ER) to PM. Besides, Aβ levels were elevated in SH-SY5Y cells after 27-OHC treatment. Our results suggest that 27-OHC motivates the transfer of astrocyte-derived cholesterol to neurons. Although there exists a feedback mechanism that excessive cholesterol promotes its conversion to 24S-OHC, the increased cholesterol induced by 27-OHC could not be wholly offset in neurons.

scholarly journals Cholesterol: Its Regulation and Role in Central Nervous System Disorders

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Matthias Orth ◽  
Stefano Bellosta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metabolic Pathways ◽  
Cholesterol Metabolism ◽  
Major Constituent ◽  
Normal Brain ◽  
Lipoprotein Receptors ◽  
Brain Cholesterol ◽  
Brain Functions ◽  
The Brain

Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

scholarly journals Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance

2021 ◽  
Author(s):  
Tatiana Pushkarsky ◽  
Adam I Ward ◽  
Dmitri Sviridov ◽  
Michael Ilya Bukrinsky
Keyword(s):  
Comparative Analysis ◽  
Lipid Rafts ◽  
Neurological Disorders ◽  
Cholesterol Metabolism ◽  
Reverse Correlation ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
The Brain ◽  
Hiv 1 ◽  
Hiv Associated Neurocognitive Disorders

HIV-associated neurological disorders (HAND) is a term used to describe a variety of neurological impairments observed in HIV-infected individuals. The pathogenic mechanisms of HAND and of its connection to HIV infection remain unknown. Previous studies suggested that HIV-1 Nef may contribute to HAND by impairing cholesterol metabolism, increasing abundance of lipid rafts and affecting their functionality. Our comparative analysis of post-mortem brain samples demonstrated a trend towards decreased abundance of cholesterol transporter ABCA1 in samples from HIV-infected ART-treated individuals relative to samples from uninfected controls, and a reverse correlation between ABCA1 and flotillin 1, a marker for lipid rafts, in all analyzed samples. The brain samples from HIV-infected individuals, both with and without HAND, were characterized by increased abundance of p-Tau217 peptide, which correlated with the abundance of flotillin 1. HIV-1 Nef was detected in some, but not all, samples from HAND-affected individuals. Samples positive for Nef had lower abundance of ABCA1, higher abundance of flotillin 1 and p-Tau217, and were obtained from individuals with higher severity of HAND relative to Nef-negative samples. These results highlight the contribution of Nef and Nef-dependent impairment of cholesterol metabolism to the pathogenesis of HAND and support a connection between pathogenesis of HAND and Alzheimer disease.

scholarly journals Cholesterol Metabolism in the Brain and Its Association with Parkinson’s Disease

2020 ◽  
Vol 29 (4) ◽  
pp. 324-324
Author(s):  
Uram Jin ◽  
Soo Jin Park ◽  
Sang Myun Park
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cholesterol Metabolism ◽  
The Brain

scholarly journals Critical Considerations on Statin Therapy

2020 ◽  
pp. 1-2
Author(s):  
Erich Ebner
Keyword(s):  
Statin Therapy ◽  
Blood Brain Barrier ◽  
Clinical Experience ◽  
Cholesterol Metabolism ◽  
Brain Barrier ◽  
Brain Cells ◽  
Blood Brain ◽  
Significant Damage ◽  
The Brain

The clinical experience, backed up by chemical analyzes, such as case observations and statistics, shows that Statin therapy entails significant damage. The focus will be on the importance of cholesterol for the functionality of the brain. The fact that brain cells show a sensitive balance of cholesterol metabolism and have to regulate their needs independently, since the blood-brain barrier does not allow the circulating blood to permeate, has to re- examine the importance and consequences of Statin therapy

scholarly journals Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

2017 ◽  
Vol 13 ◽  
pp. 720-727 ◽  
Author(s):  
Malte Hilsch ◽  
Ivan Haralampiev ◽  
Peter Müller ◽  
Daniel Huster ◽  
Holger A Scheidt
Keyword(s):  
Nmr Spectroscopy ◽  
Membrane Permeability ◽  
Alkyl Chain ◽  
Cholesterol Metabolism ◽  
Membrane Properties ◽  
H Nmr ◽  
Chain Order ◽  
Lipid Chain ◽  
The Brain ◽  
Permeability Assay

Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group in the alkyl chain and are able to efficiently cross the brain–blood barrier. Therefore, they are responsible for the sterol transfer between brain and circulation. The current study compares the membrane properties of several hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a membrane permeability assay, and fluorescence microscopy experiments. It is shown that hydroxycholesterols do not exert the unique impact on membrane properties characteristic for cholesterol with regard to the influence on lipid chain order, membrane permeability and formation of lateral domains.

scholarly journals Markers of Cholesterol Metabolism in the Brain Show Stronger Associations with Cerebrovascular Disease than Alzheimer's Disease

2012 ◽  
Vol 30 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Timothy M. Hughes ◽  
Lewis H. Kuller ◽  
Oscar L. Lopez ◽  
James T. Becker ◽  
Rhobert W. Evans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Cholesterol Metabolism ◽  
The Brain

Benzodiazepine Receptors in the Periphery

2020 ◽  
pp. 81-96
Author(s):  
Robert B. Raffa
Keyword(s):  
Immune Function ◽  
Cholesterol Metabolism ◽  
Benzodiazepine Receptors ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Pharmacologic Effect ◽  
Ion Influx ◽  
Transmembrane Potential Difference ◽  
The Brain

The benzodiazepines are almost universally thought to produce one and only one pharmacologic effect: positive allosteric modulation of GABAA receptors located in the brain. This results in an increased Cl−ion influx, greater negative transmembrane potential difference, and neurons that are less likely to fire in response to anxiety-producing stimulation. Unfortunately, the simplicity and success of this mono-target belief has distracted researchers and clinicians from studying and appreciating their other pharmacology. A glaring example is the general lack of awareness of the peripheral benzodiazepine receptor. The peripheral benzodiazepine receptor alters mitochondrial function (energy supply), cholesterol transport, and immune function. A patient who is on long-term benzodiazepine therapy (or withdrawing from them) will have these sites affected, just as are the sites located in the brain. One can easily imagine that the adverse effects associated with the peripheral sites would be fundamental, varied, and potentially profound—involving lack of energy, altered cholesterol metabolism, and aberrant immune function.

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