Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

doi:10.1002/jcp.25488

Cited by 65 publications

(41 citation statements)

References 98 publications

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“…44 In the brain, cholesterol is either incorporated into the cell membrane, where it regulates signal transduction pathways, or influences synapse formation, action potentials and neurotransmitter release. 45 Furthermore, intracellular cholesterol serves as the precursor for the synthesis of many neurosteroids that are synthesized in the brain, such as allopregnanolone. 45 One of the major ways in which the brain clears cholesterol is via its conversion to 24-(S)-hydroxycholesterol, a reaction catalyzed by the enzyme Cytochrome p450 46A1 (Cyp46A1).…”

Section: Effect Of Bile Acids On Neuronal Dysfunctionmentioning

confidence: 99%

“…45 Furthermore, intracellular cholesterol serves as the precursor for the synthesis of many neurosteroids that are synthesized in the brain, such as allopregnanolone. 45 One of the major ways in which the brain clears cholesterol is via its conversion to 24-(S)-hydroxycholesterol, a reaction catalyzed by the enzyme Cytochrome p450 46A1 (Cyp46A1). 46 24-(S)-hydroxycholesterol is then able to exit the brain and enter the blood stream where it is integrated into the de novo bile acid synthesis pathway in the liver.…”

Section: Effect Of Bile Acids On Neuronal Dysfunctionmentioning

confidence: 99%

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Bile Acids in Hepatic Encephalopathy

DeMorrow

2019

Journal of Clinical and Experimental Hepatology

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TX 76504, USA and y Central Texas Veterans Healthcare System, Temple, TX 76504, USA Hepatic encephalopathy describes the array of neurological complications that arise due to liver insufficiency and/or portal-systemic shunt. The pathogenesis of hepatic encephalopathy shares a longstanding association with hyperammonemia and inflammation. Recently, aberrant bile acid signaling has been implicated in the development of key features of hepatic encephalopathy due to acute liver failure including neuronal dysfunction, neuroinflammation and blood-brain barrier permeability. This review summarizes the findings of recent studies demonstrating a role for bile acids in hepatic encephalopathy and speculates on the possible downstream consequences of bile acid signaling. ( J CLIN EXP HEPATOL 2019;9:117-124) Keywords: blood-brain barrier, farnesoid X receptor, neuroinflammation, sphingosine-1-phosphate receptor 2, Takeda G-protein coupled receptor 5 (TGR5)

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Section: Effect Of Bile Acids On Neuronal Dysfunctionmentioning

confidence: 99%

Section: Effect Of Bile Acids On Neuronal Dysfunctionmentioning

confidence: 99%

Bile Acids in Hepatic Encephalopathy

DeMorrow

2019

Journal of Clinical and Experimental Hepatology

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“…Many of the post-TBI changes in lipids that have been described involve alterations in blood and brain polyunsaturated fatty acids (PUFA)-containing PLs required for maintaining membrane integrity and synaptogenesis (Liu et al, 2015;Emmerich et al, 2017;Knobloch, 2017;Fiandaca et al, 2018). Lipid associated factors such as cholesterol may be peripherally altered in TBI as, under normal physiological conditions, brain cholesterol is compartmentalized and restricted to the brain by the presence of the blood brain barrier (BBB) (Cartocci et al, 2016); however, BBB disturbances after TBI (Sulhan et al, 2018) may alter the brain's cholesterol content by allowing an exchange between peripheral and CNS cholesterol pools which may in turn adversely affect neuronal function. Studies have shown that CSF cholesterol increases acutely after TBI (Kay et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

et al. 2020

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The differential diagnosis between mild Traumatic Brain Injury (mTBI) sequelae and Post-Traumatic Stress Disorder (PTSD) is challenging due to their symptomatic overlap and co-morbidity. As such, there is a need to develop biomarkers which can help with differential diagnosis of these two conditions. Studies from our group and others suggest that blood and brain lipids are chronically altered in both mTBI and PTSD. Therefore, examining blood lipids presents a minimally invasive and cost-effective approach to identify promising biomarkers of these conditions. Using liquid chromatography-mass spectrometry (LC-MS) we examined hundreds of lipid species in the blood of healthy active duty soldiers (n = 52) and soldiers with mTBI (n = 21), PTSD (n = 34) as well as co-morbid mTBI and PTSD (n = 13) to test whether lipid levels were differentially altered with each. We also examined if the apolipoprotein E (APOE) ε4 allele can affect the association between diagnosis and peripheral lipid levels in this cohort. We show that several lipid classes are altered with diagnosis and that there is an interaction between diagnosis and the ε4 carrier status on these lipids. Indeed, total lipid levels as well as both the degree of unsaturation and chain lengths are differentially altered with diagnosis and ε4 status, specifically long chain unsaturated triglycerides (TG) and both saturated and mono-unsaturated diglycerides (DG). Additionally, an examination of lipid species reveals distinct profiles in each diagnostic group stratified by ε4 status, mainly in TG, saturated DG species and polyunsaturated phosphatidylserines. In summary, we show that peripheral lipids are promising biomarker candidates to assist with the differential diagnosis of mTBI and PTSD. Further, ε4 carrier status alone and in interaction with diagnosis has a strong influence on peripheral lipid levels. Therefore, examining ε4 status along with peripheral lipid levels could help with differential diagnosis of mTBI and PTSD.

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“…Cholesterol is an indispensable building block for all cell membranes and is incorporated in considerable amounts into myelin in the nervous system during the period of rapid brain growth, and it serves as the substrate for the synthesis of bile acids, lipoproteins, vitamin D, hormones, and oxysterols that modulate cholesterol, lipid, and glucose homeostasis [3,9,[17][18][19] . The provision of cholesterol with breastfeeding is associated with higher plasma concentrations of total and low-density lipoprotein cholesterol in breastfed than in formula-fed infants [20] .…”

Section: Cholesterolmentioning

confidence: 99%

Human Milk Lipids

2016

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Human milk lipids provide the infant with energy and essential vitamins, polyunsaturated fatty acids, and bioactive components. Adding complex lipids and milk fat globule membranes to vegetable oil-based infant formula has the potential to enhance infant development and reduce infections. Cholesterol provision with breastfeeding modulates infant sterol metabolism and may induce long-term benefits. Some 98-99% of milk lipids are comprised by triacylglycerols, whose properties depend on incorporated fatty acids. Attention has been devoted to the roles of the long-chain polyunsaturated fatty acids docosahexaenoic (DHA) and arachidonic (ARA) acids. Recent studies on gene-diet interaction (Mendelian randomization) show that breastfeeding providing DHA and ARA improves cognitive development and reduces asthma risk at school age particularly in those children with a genetically determined lower activity of DHA and ARA synthesis. It appears prudent to follow the biological model of human milk in the design of infant formula as far as feasible, unless conclusive evidence for the suitability and safety of other choices is available. The recent European Union legislative stipulation of a high formula DHA content without required ARA deviates from this concept, and such a novel formula composition has not been adequately evaluated. Great future opportunities arise with significant methodological progress for example in lipidomic analyses and their bioinformatic evaluation, which should enhance understanding of the biology of human milk lipids. Such knowledge might lead to improved dietary advice to lactating mothers as well as to further opportunities to enhance infant formula composition.

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Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

Cited by 65 publications

References 98 publications

Bile Acids in Hepatic Encephalopathy

Bile Acids in Hepatic Encephalopathy

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

Human Milk Lipids

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