دورية أكاديمية
Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer's Disease in 3xTg-AD Mice.
| العنوان: | Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer's Disease in 3xTg-AD Mice. |
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| المؤلفون: | Hu XH; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Yu KY; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Li XX; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Zhang JN; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Jiao JJ; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Wang ZJ; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China., Cai HY; Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, People's Republic of China., Wang L; Department of Geriatrics, Shanxi Bethune Hospital, Taiyuan, People's Republic of China., He YX; Department of Radiology, Shanxi Provincial People's Hospital, Taiyuan, People's Republic of China., Wu MN; Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Key Laboratory of Cellular Physiology in Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China. |
| المصدر: | The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2024 Jul 01; Vol. 79 (7). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: published on behalf of the Gerontological Society of America by Oxford University Press Country of Publication: United States NLM ID: 9502837 Publication Model: Print Cited Medium: Internet ISSN: 1758-535X (Electronic) Linking ISSN: 10795006 NLM ISO Abbreviation: J Gerontol A Biol Sci Med Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : published on behalf of the Gerontological Society of America by Oxford University Press Original Publication: Washington, DC : Gerontological Society of America, c1995- |
| مواضيع طبية MeSH: | Alzheimer Disease*/metabolism , Alzheimer Disease*/drug therapy , Alzheimer Disease*/pathology , Disease Models, Animal* , Mice, Transgenic* , Orexin Receptor Antagonists*/pharmacology , Disease Progression* , Cognitive Dysfunction*/drug therapy, Animals ; Mice ; Orexin Receptors/metabolism ; Amyloid beta-Peptides/metabolism ; Male ; Hippocampus/drug effects ; Hippocampus/pathology ; Hippocampus/metabolism |
| مستخلص: | The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aβ deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated. (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| معلومات مُعتمدة: | 82271484 National Natural Science Foundation of China; 2020-083 Shanxi Scholarship Council of China |
| فهرسة مساهمة: | Keywords: MK-1064; Neuroinflammation; Synaptic plasticity; β-Amyloid protein |
| المشرفين على المادة: | 0 (Orexin Receptor Antagonists) 0 (Orexin Receptors) 0 (Amyloid beta-Peptides) |
| تواريخ الأحداث: | Date Created: 20240429 Date Completed: 20240607 Latest Revision: 20240608 |
| رمز التحديث: | 20240608 |
| DOI: | 10.1093/gerona/glae115 |
| PMID: | 38682858 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1758-535X |
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| DOI: | 10.1093/gerona/glae115 |