Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters
The retina and brain are separated from the systemic circulation by the anatomical barriers, which are permeable (the outer blood-retinal barrier) and impermeable (the blood-brain and inner blood-retina barriers) to cholesterol. Herein we investigated whether whole-body cholesterol maintenance affec...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000743 |
| _version_ | 1797776262845956096 |
|---|---|
| author | Natalia Mast Nicole El-Darzi Yong Li Irina A. Pikuleva |
| author_facet | Natalia Mast Nicole El-Darzi Yong Li Irina A. Pikuleva |
| author_sort | Natalia Mast |
| collection | DOAJ |
| description | The retina and brain are separated from the systemic circulation by the anatomical barriers, which are permeable (the outer blood-retinal barrier) and impermeable (the blood-brain and inner blood-retina barriers) to cholesterol. Herein we investigated whether whole-body cholesterol maintenance affects cholesterol homeostasis in the retina and brain. We used hamsters, whose whole-body cholesterol handling is more similar to those in humans than in mice, and conducted separate administrations of deuterated water and deuterated cholesterol. We assessed the quantitative significance of the retinal and brain pathways of cholesterol input and compared the results with those from our previous studies in mice. The utility of the measurements in the plasma of deuterated 24-hydroxycholesterol, the major cholesterol elimination product from the brain, was investigated as well. We established that despite a sevenfold higher serum LDL to HDL ratio and other cholesterol-related differences, in situ biosynthesis remained the major source of cholesterol for hamster retina, although its quantitative significance was reduced to 53% as compared to 72%–78% in the mouse retina. In the brain, the principal pathway of cholesterol input was also the same, in situ biosynthesis, accounting for 94% of the total brain cholesterol input (96% in mice); the interspecies differences pertained to the absolute rates of the total cholesterol input and turnover. We documented the correlations between deuterium enrichments of the brain 24-hydroxycholesterol, brain cholesterol, and plasma 24-hydroxycholesterol, which suggested that deuterium enrichment of plasma 24-hydroxycholesteol could be an in vivo marker of cholesterol elimination and turnover in the brain. |
| first_indexed | 2024-03-12T22:47:08Z |
| format | Article |
| id | doaj.art-5dec79429d9b43af9231e30c0cf209b6 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-12T22:47:08Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-5dec79429d9b43af9231e30c0cf209b62023-07-21T04:57:39ZengElsevierJournal of Lipid Research0022-22752023-07-01647100401Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamstersNatalia Mast0Nicole El-Darzi1Yong Li2Irina A. Pikuleva3Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USADepartment of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USADepartment of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USAFor correspondence: Irina A. Pikuleva; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USAThe retina and brain are separated from the systemic circulation by the anatomical barriers, which are permeable (the outer blood-retinal barrier) and impermeable (the blood-brain and inner blood-retina barriers) to cholesterol. Herein we investigated whether whole-body cholesterol maintenance affects cholesterol homeostasis in the retina and brain. We used hamsters, whose whole-body cholesterol handling is more similar to those in humans than in mice, and conducted separate administrations of deuterated water and deuterated cholesterol. We assessed the quantitative significance of the retinal and brain pathways of cholesterol input and compared the results with those from our previous studies in mice. The utility of the measurements in the plasma of deuterated 24-hydroxycholesterol, the major cholesterol elimination product from the brain, was investigated as well. We established that despite a sevenfold higher serum LDL to HDL ratio and other cholesterol-related differences, in situ biosynthesis remained the major source of cholesterol for hamster retina, although its quantitative significance was reduced to 53% as compared to 72%–78% in the mouse retina. In the brain, the principal pathway of cholesterol input was also the same, in situ biosynthesis, accounting for 94% of the total brain cholesterol input (96% in mice); the interspecies differences pertained to the absolute rates of the total cholesterol input and turnover. We documented the correlations between deuterium enrichments of the brain 24-hydroxycholesterol, brain cholesterol, and plasma 24-hydroxycholesterol, which suggested that deuterium enrichment of plasma 24-hydroxycholesteol could be an in vivo marker of cholesterol elimination and turnover in the brain.http://www.sciencedirect.com/science/article/pii/S0022227523000743hamsterretinabraincholesterol biosynthesis24-hydroxycholesteroldeuterium enrichment |
| spellingShingle | Natalia Mast Nicole El-Darzi Yong Li Irina A. Pikuleva Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters Journal of Lipid Research hamster retina brain cholesterol biosynthesis 24-hydroxycholesterol deuterium enrichment |
| title | Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters |
| title_full | Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters |
| title_fullStr | Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters |
| title_full_unstemmed | Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters |
| title_short | Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters |
| title_sort | quantitative characterizations of the cholesterol related pathways in the retina and brain of hamsters |
| topic | hamster retina brain cholesterol biosynthesis 24-hydroxycholesterol deuterium enrichment |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000743 |
| work_keys_str_mv | AT nataliamast quantitativecharacterizationsofthecholesterolrelatedpathwaysintheretinaandbrainofhamsters AT nicoleeldarzi quantitativecharacterizationsofthecholesterolrelatedpathwaysintheretinaandbrainofhamsters AT yongli quantitativecharacterizationsofthecholesterolrelatedpathwaysintheretinaandbrainofhamsters AT irinaapikuleva quantitativecharacterizationsofthecholesterolrelatedpathwaysintheretinaandbrainofhamsters |