Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease
BackgroundAmyloid-β protein (Aβ) accumulation is a defining characteristic of Alzheimer’s disease (AD), resulting in neurodegeneration and a decline in cognitive function. Given orexin’s well-documented role in enhancing memory and cognition, this study investigates its potential to regulate Aβ-indu...
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Frontiers Media S.A.
2025-03-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1529981/full |
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| author | Chenyu Zhuang Hengyu Yan Jiayu Lu Yifan Zhou Yanqing Liu Yanqing Liu Guoshan Shi Yan Li Yan Li Yan Li Yan Li |
| author_facet | Chenyu Zhuang Hengyu Yan Jiayu Lu Yifan Zhou Yanqing Liu Yanqing Liu Guoshan Shi Yan Li Yan Li Yan Li Yan Li |
| author_sort | Chenyu Zhuang |
| collection | DOAJ |
| description | BackgroundAmyloid-β protein (Aβ) accumulation is a defining characteristic of Alzheimer’s disease (AD), resulting in neurodegeneration and a decline in cognitive function. Given orexin’s well-documented role in enhancing memory and cognition, this study investigates its potential to regulate Aβ-induced neurotoxicity, offering new perspectives into AD management.MethodsThis paper simulated Aβ accumulation in the hippocampus of AD patients by administering Aβ1-42 oligomers into the bilateral hippocampal dentate gyrus of ICR mice. Inflammatory cytokines (IL-6, TNF-α) and orexin-A levels were measured by ELISA. Additionally, the excitability of orexinergic neurons was assessed by IHC targeting c-Fos expression. These methodologies evaluated the Aβ-induced neuroinflammation, orexinergic system functionality, and dexamethasone’s (Dex) effects on these processes.ResultsInjection of Aβ1-42 oligomer resulted in elevated levels of IL-6, TNF-α, and orexin-A in the hippocampus, as well as increased excitability of orexinergic neurons in the lateral hypothalamus (LH). Dex treatment reduced neuroinflammation, causing a reduction in orexin-A levels and the excitability of orexinergic neurons.ConclusionAβ-induced neuroinflammation is accompanied by enhanced levels of orexin-A and orexinergic neuron excitability. These findings suggest that the enhanced functionality of the orexinergic system may become a compensatory neuroprotective mechanism to counteract neuroinflammation and enhance cognitive function. |
| format | Article |
| id | doaj-art-3670ca6327ec4006816879e4a8ae41fa |
| institution | Kabale University |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-3670ca6327ec4006816879e4a8ae41fa2025-08-20T03:39:57ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-03-011610.3389/fphys.2025.15299811529981Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s diseaseChenyu Zhuang0Hengyu Yan1Jiayu Lu2Yifan Zhou3Yanqing Liu4Yanqing Liu5Guoshan Shi6Yan Li7Yan Li8Yan Li9Yan Li10Medical College, Yangzhou University, Yangzhou, ChinaMedical College, Yangzhou University, Yangzhou, ChinaMedical College, Yangzhou University, Yangzhou, ChinaMedical College, Yangzhou University, Yangzhou, ChinaMedical College, Yangzhou University, Yangzhou, ChinaThe Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, ChinaDepartment of Basic Medical Sciences, Guizhou University of Chinese Medicine, Guiyang, ChinaMedical College, Yangzhou University, Yangzhou, ChinaThe Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, ChinaDepartment of Traditional Chinese Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, ChinaBackgroundAmyloid-β protein (Aβ) accumulation is a defining characteristic of Alzheimer’s disease (AD), resulting in neurodegeneration and a decline in cognitive function. Given orexin’s well-documented role in enhancing memory and cognition, this study investigates its potential to regulate Aβ-induced neurotoxicity, offering new perspectives into AD management.MethodsThis paper simulated Aβ accumulation in the hippocampus of AD patients by administering Aβ1-42 oligomers into the bilateral hippocampal dentate gyrus of ICR mice. Inflammatory cytokines (IL-6, TNF-α) and orexin-A levels were measured by ELISA. Additionally, the excitability of orexinergic neurons was assessed by IHC targeting c-Fos expression. These methodologies evaluated the Aβ-induced neuroinflammation, orexinergic system functionality, and dexamethasone’s (Dex) effects on these processes.ResultsInjection of Aβ1-42 oligomer resulted in elevated levels of IL-6, TNF-α, and orexin-A in the hippocampus, as well as increased excitability of orexinergic neurons in the lateral hypothalamus (LH). Dex treatment reduced neuroinflammation, causing a reduction in orexin-A levels and the excitability of orexinergic neurons.ConclusionAβ-induced neuroinflammation is accompanied by enhanced levels of orexin-A and orexinergic neuron excitability. These findings suggest that the enhanced functionality of the orexinergic system may become a compensatory neuroprotective mechanism to counteract neuroinflammation and enhance cognitive function.https://www.frontiersin.org/articles/10.3389/fphys.2025.1529981/fullAlzheimer’s diseaseorexin (hypocretin)amyloid-β proteincognitive impairmentneuroprotection |
| spellingShingle | Chenyu Zhuang Hengyu Yan Jiayu Lu Yifan Zhou Yanqing Liu Yanqing Liu Guoshan Shi Yan Li Yan Li Yan Li Yan Li Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease Frontiers in Physiology Alzheimer’s disease orexin (hypocretin) amyloid-β protein cognitive impairment neuroprotection |
| title | Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease |
| title_full | Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease |
| title_fullStr | Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease |
| title_full_unstemmed | Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease |
| title_short | Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer’s disease |
| title_sort | compensatory enhancement of orexinergic system functionality induced by amyloid β protein a neuroprotective response in alzheimer s disease |
| topic | Alzheimer’s disease orexin (hypocretin) amyloid-β protein cognitive impairment neuroprotection |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1529981/full |
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