Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition
Open accessAbstract
Dysregulated cholesterol metabolism is a major risk factor for atherosclerosis and other late-onset disorders, such as Alzheimer's disease. The scavenger receptor, class B, type I (SR-BI) is critical in maintaining the homeostasis of cholesterol and alpha-tocopherol. SR-BI binds high-density lipoproteins (HDL) and mediates the selective transfer of cholesteryl esters and alpha-tocopherol from circulating HDL to cells. SR-BI is also involved in reverse cholesterol transport from peripheral tissues into the liver. Previous studies using SR-BI genetic knockout mice indicated that the deletion of SR-BI resulted in an accelerated onset of atherosclerosis. We hypothesized that SR-BI-dependent lipid dysregulation might disrupt brain function leading to cognitive impairment. Here, we report that very old SR-BI knockout mice show deficient synaptic plasticity (long-term potentiation) in the CA1 region of the hippocampus. Very old SR-BI KO mice also display selective impairments in recognition memory and spatial memory. Thus, SR-BI influences neural and cognitive processes, a finding that highlights the contribution of cholesterol and alpha-tocopherol homeostasis in proper cognitive function.
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Recent studies suggest that impaired angiogenesis in patients with hypercholesterolaemia parallels disturbances in synaptic plasticity, though evidence is limited.
“Although evidence is limited, recent studies suggest that impaired angiogenesis in patients with hypercholesterolaemia parallels disturbances in synaptic plasticity.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [86]
In hypercholesterolaemic mice lacking scavenger receptor class B type I, age-related spatial memory deficits were accompanied by impaired long-term potentiation of hippocampal CA1 neurons.
“In hypercholesterolaemic mice lacking scavenger receptor class B type I, age-related deficits of spatial memory have been described that were accompanied by impaired long-term potentiation of hippocampal CA1 neurons.86”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [86]
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- Authors
- Chang, E. H., Rigotti, A., & Huerta, P. T.
- Affiliations
- Cornell University (US)
- Pontificia Universidad Católica de Chile (CL)
- Corresponding author
- Huerta, Patricio T.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 30
- Issue
- 3
- Pages
- 407-419
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2665297
- OpenAlex
- W2105168017
- Cited by
- 35
- References
- 85
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 1 · 2012: 2
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01AI073693)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- scavenger receptor class B type I, HDL cholesterol, cholesterol metabolism, alpha-tocopherol, synaptic plasticity, long-term potentiation, hippocampal CA1, cognitive impairment, memory impairment, atherosclerosis, Alzheimer's disease, reverse cholesterol transport, age-related cognitive decline
- MeSH terms
- Aging, Animals, Cholesterol, Cognition, Female, Homeostasis, Lipoproteins, HDL, Male, Mice, Inbred C57BL, Neuronal Plasticity, Organ Culture Techniques, Synapses, Receptors, Lipoprotein, Mice, Knockout, alpha-Tocopherol, Scavenger Receptors, Class B, Mice
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