Analysis of oxysterols and vitamin D metabolites in mouse brain and cell line samples by ultra-high-performance liquid chromatography-atmospheric pressure photoionization–mass spectrometry

Ahonen, Linda; Maire, Florian; Savolainen, Mari; Kopra, Jaakko; Vreeken, Rob J.; Hankemeier, Thomas; Myöhänen, Timo T.; Kylli, Petri; Kostiainen, Risto

doi:10.1016/j.chroma.2014.08.088

Cited by 34 publications

(39 citation statements)

References 44 publications

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“…Of note, the study authors observed that the levels of potentially amyloidogenic sterol species derived from the auto-oxidation of cholesterol, like β-EPOX, were higher at the mild cognitive impairment disease stage. Oxysterols have also been identified in mouse brains and, in addition to the above cited cholesterol derivatives, consistent levels of 25-hydroxycholesterol (25-OH) were found (Ahonen et al, 2014). Increased levels of 24-OH, 7-K, and β-EPOX have also been detected in areas of the rat hippocampus undergoing gliosis and neuroinflammation, after excitotoxic injury (He et al, 2006; Kim et al, 2010).…”

Section: The Involvement Of Oxysterols In Ad Pathogenesismentioning

confidence: 93%

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

Gamba

Testa

Gargiulo

et al. 2015

Front. Aging Neurosci.

167

155

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Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid Aβ peptides and neurofibrillary tangles (NFT) within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism. The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier (BBB). The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death. This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis.

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Section: The Involvement Of Oxysterols In Ad Pathogenesismentioning

confidence: 93%

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

Gamba

Testa

Gargiulo

et al. 2015

Front. Aging Neurosci.

167

155

View full text Add to dashboard Cite

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“…Oxysterol extraction methods were adapted from Ahonen et al [35]. Briefly, 1 mL of methyl t-butyl ether (MTBE) was added to a 150 μL of rabbit serum.…”

Section: Methodsmentioning

confidence: 99%

“…Methods of oxysterol extraction from the brain were developed based on Ahonen et al [35]. Briefly, the intact left hippocampi were weighed and homogenized using ultrasonication, and 0.5 mL dichloromethane (DCM): methanol mixture (1 : 1, v/v) was added to tissue and sonicated on an ice bath for 1 min.…”

Section: Methodsmentioning

confidence: 99%

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Brooks

Dykes

Schreurs

2017

JAD

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Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer’s disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients. Dietary cholesterol, which cannot pass the blood-brain barrier, is thought to influence central nervous system homeostasis by increased transport of its circulatory breakdown product, 27-hydroxycholesterol (27-OHC), into the brain. 27-OHC is an endogenous selective estrogen receptor modulator. Estrogen-mediated non-reproductive functions require estrogen receptors (ERs) and include modulation of mitochondrial function and structure, as well as regulation of synaptogenesis in the brain. ERs are located in brain areas affected early in AD pathogenesis, including the hippocampus. Here we report that increase in serum cholesterol, induced by feeding rabbits a high-cholesterol diet, is associated with higher levels of 27-OHC in the brain as well as increased levels of neurodegeneration in the hippocampus. Furthermore, these results are accompanied by changes in expression of ERs in the hippocampus as well as a decrease in hippocampal mitochondria. These findings provide an important insight into one of the possible mechanisms involved in the development of AD, and shed light on the processes that may antedate amyloid-β and tau phosphorylation changes currently hypothesized to cause AD symptomology and pathology.

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“…Thus, for measuring native oxysterols in larger samples microbore/conventional columns e.g. [16,18,22] should be safe to use regarding carry-over. On the other hand, for analysis of very limited samples (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…This was partly inspired by the study of McDonald et al [10] who could monitor oxysterolssalt complexes (along with a number of other lipids) in biological samples using ESI and an AB Sciex API 5000 triple quadrupole mass spectrometer without derivatization. Other ionization sources such as APPI [16] and APCI [17,18] were not considered as they are not compatible with the low flow used in nanoLC.…”

Section: Introductionmentioning

confidence: 99%

Underivatized oxysterols and nanoLC–ESI-MS: A mismatch

et al. 2015

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Analysis of oxysterols and vitamin D metabolites in mouse brain and cell line samples by ultra-high-performance liquid chromatography-atmospheric pressure photoionization–mass spectrometry

Cited by 34 publications

References 44 publications

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Underivatized oxysterols and nanoLC–ESI-MS: A mismatch

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