Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice
Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementati...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7580 |
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| author | Alejandro Sánchez-Melgar Pedro J. Izquierdo-Ramírez Christian Griñán-Ferré Mercè Pallàs Mairena Martín José Luis Albasanz |
| author_facet | Alejandro Sánchez-Melgar Pedro J. Izquierdo-Ramírez Christian Griñán-Ferré Mercè Pallàs Mairena Martín José Luis Albasanz |
| author_sort | Alejandro Sánchez-Melgar |
| collection | DOAJ |
| description | Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing. |
| first_indexed | 2024-03-09T03:22:01Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:22:01Z |
| publishDate | 2022-07-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-eef6f018ef9c4ce7b4af83e7f4e4fad82023-12-03T15:09:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314758010.3390/ijms23147580Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 MiceAlejandro Sánchez-Melgar0Pedro J. Izquierdo-Ramírez1Christian Griñán-Ferré2Mercè Pallàs3Mairena Martín4José Luis Albasanz5Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 13071 Ciudad Real, SpainDepartment of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 13071 Ciudad Real, SpainDepartment of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona, 08028 Barcelona, SpainDepartment of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 13071 Ciudad Real, SpainDepartment of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 13071 Ciudad Real, SpainCholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing.https://www.mdpi.com/1422-0067/23/14/7580Alzheimer’s diseaseantioxidantscell signalingreceptors/seven transmembrane domainlipoproteins |
| spellingShingle | Alejandro Sánchez-Melgar Pedro J. Izquierdo-Ramírez Christian Griñán-Ferré Mercè Pallàs Mairena Martín José Luis Albasanz Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice International Journal of Molecular Sciences Alzheimer’s disease antioxidants cell signaling receptors/seven transmembrane domain lipoproteins |
| title | Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice |
| title_full | Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice |
| title_fullStr | Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice |
| title_full_unstemmed | Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice |
| title_short | Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice |
| title_sort | neuroprotective effects of resveratrol by modifying cholesterol metabolism and aβ processing in samp8 mice |
| topic | Alzheimer’s disease antioxidants cell signaling receptors/seven transmembrane domain lipoproteins |
| url | https://www.mdpi.com/1422-0067/23/14/7580 |
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