| 1. |
- Simancas, J.F., et al.
(author)
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The seismic crustal structure of the Ossa-Morena Zone and its geological interpretation
- 2004
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In: Journal of Iberian Geology. - 1698-6180 .- 1886-7995. ; 30, s. 133-142
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Journal article (peer-reviewed)abstract
- The IBERSEIS deep reflection seismic experiment has provided a crustal image of the Variscan orogen of southwest Iberia. A brief presentation of the entire seismic profile is given, and then the Ossa-Morena Zone (OMZ) and its boundaries are considered. The crust of the OMZ is shown to be divided into an upper crust, characterized by dominantly NE-dipping reflectivity, and a poorly reflective lower crust. The reflectivity of the upper crust has good correlation with the geological cross-section constructed from surface mapping. In the seismic image, the upper crustal geological structures are seen to merge in the middle crust. Nevertheless, the OMZ middle crust is not a mere detachment level, as it shows very unusual features: it appears as a band of strong reflectivity and irregular thickness (the Iberian Reflective Body, IRB) that we interpret as a great sill-like intrusion of basic rocks. The boundaries of the OMZ are considered sutures of the orogen, and their geometrical features, as deduced from geological mapping and the seismic image, are in accordance with the transpressional character of the Variscan collision recorded in SW Iberia. The present Moho is flat, obliterating the root of the orogen.
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| 2. |
- Ismail, MA, et al.
(author)
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27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation
- 2017
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:3, s. 699-717
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Journal article (peer-reviewed)abstract
- Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.
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| 5. |
- Loera-Valencia, R, et al.
(author)
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Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration
- 2021
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In: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 58:12, s. 6063-6076
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Journal article (peer-reviewed)abstract
- Alterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer’s disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown. We used a high-fat/high-cholesterol diet in mice to study the effects of hypercholesterolemia over the alarmin S100A8 cascade in the hippocampus. Using CYP27Tg, a transgenic mouse model, we show that the hypercholesterolemia influence on the brain is mediated by the excess of 27-hydroxycholesterol (27-OH), a cholesterol metabolite. We also employed an acute model of 27-OH intraventricular injection in the brain to study RAGE and S100A8 response. We used primary cultures of neurons and astrocytes to study the effect of high levels of 27-OH over the S100A8 alarmin cascade. We report that a high-fat/high-cholesterol diet leads to an increase in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects of hypercholesterolemia to the brain via alarmin signaling.
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