ArticleInternational journal of molecular sciences2022
Regulation of Th17/Treg Balance by 27-Hydroxycholesterol and 24S-Hydroxycholesterol Correlates with Learning and Memory Ability in Mice.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Microbiota-gut-brain axis and bile acids-driven neuromodulation.Neural regeneration research · 2026Article
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Dietary mixed-oxysterols and 27-Hydroxycholesterol induce cognitive impairment by regulating gut microbiota and miR-144-3p in vivo.GeroScience · 2026Article
- Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- Identifying Oxysterols Associated With Age and Diet in Mice Using Optimized Reversed-phase Liquid Chromatography-Mass Spectrometry (RPLC-MS).Journal of separation science · 2025Article
- The Link Between Oxysterols and Gut Microbiota in the Co-Dysfunction of Cognition and Muscle.Nutrients · 2025Article
- The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson's disease.PLoS biology · 2025Article
- Quantitative Determination of a Series of Oxysterols by an Optimized LC-MS/MS Analysis in Different Tissue Types.International journal of molecular sciences · 2024Article
- Article
- Review
- Calycosin-7-O-β-D-Glucoside Ameliorates Palmitate-Induced Lipid Accumulation in HT22 Cells.Actas espanolas de psiquiatria · 2024Article
- Article
- Review
- The impact of maternal anti-inflammatory drugs on surgical anesthesia-induced neuroinflammation and cognitive impairment in offspring mice.Frontiers in cellular neuroscience · 2024Article
- 27-Hydroxycholesterol-Induced Dysregulation of Cholesterol Metabolism Impairs Learning and Memory Ability in ApoE ε4 Transgenic Mice.International journal of molecular sciences · 2022Article
- Regulatory T Cell Therapeutics for Neuroinflammatory Disorders.Critical reviews in immunology · 2022Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of cholesterol metabolism and its oxidative products-oxysterols-in the brain is known to be associated with neurodegenerative diseases. It is well-known that 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) are the main oxysterols contributing to the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of how 27-OHC and 24S-OHC cause cognitive decline remains unclear. To verify whether 27-OHC and 24S-OHC affect learning and memory by regulating immune responses, C57BL/6J mice were subcutaneously injected with saline, 27-OHC, 24S-OHC, 27-OHC+24S-OHC for 21 days. The oxysterols level and expression level of related metabolic enzymes, as well as the immunomodulatory factors were measured. Our results indicated that 27-OHC-treated mice showed worse learning and memory ability and higher immune responses, but lower expression level of interleukin-10 (IL-10) and interferon (IFN-λ2) compared with saline-treated mice, while 24S-OHC mice performed better in the Morris water maze test than control mice. No obvious morphological lesion was observed in these 24S-OHC-treated mice. Moreover, the expression level of interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 3α (MIP-3α) were significantly decreased after 24S-OHC treatment. Notably, compared with 27-OHC group, mice treated with 27-OHC+24S-OHC showed higher brain 24S-OHC level, accompanied by increased CYP46A1 expression level while decreased CYP7B1, retinoic acid-related orphan receptor gamma t (RORγt) and IL-17A expression level. In conclusion, our study indicated that 27-OHC is involved in regulating the expression of RORγt, disturbing Th17/Treg balance-related immune responses which may be associated with the learning and memory impairment in mice. In contrast, 24S-OHC is neuroprotective and attenuates the neurotoxicity of 27-OHC.
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