Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease
Sleep disturbances are common in Alzheimer’s disease (AD) and AD-related dementia (ADRD). We performed a sleep study on Tg-SwDI mice, a cerebral amyloid angiopathy (CAA) model, and age-matched wild-type (WT) control mice. The results showed that at 12 months of age, the hemizygous Tg-SwDI mice spent...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| author | Yan Wu Narayan R. Bhat Meng Liu |
| author_facet | Yan Wu Narayan R. Bhat Meng Liu |
| author_sort | Yan Wu |
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| description | Sleep disturbances are common in Alzheimer’s disease (AD) and AD-related dementia (ADRD). We performed a sleep study on Tg-SwDI mice, a cerebral amyloid angiopathy (CAA) model, and age-matched wild-type (WT) control mice. The results showed that at 12 months of age, the hemizygous Tg-SwDI mice spent significantly more time in non-rapid eye movement (NREM) sleep (44.6 ± 2.4% in Tg-SwDI versus 35.9 ± 2.5% in WT) and had a much shorter average length of wake bout during the dark (active) phase (148.5 ± 8.7 s in the Tg-SwDI versus 203.6 ± 13.0 s in WT). Histological analysis revealed stark decreases of orexin immunoreactive (orexin-IR) neuron number and soma size in these Tg-SwDI mice (cell number: 2187 ± 97.1 in Tg-SwDI versus 3318 ± 137.9 in WT. soma size: 109.1 ± 8.1 μm2 in Tg-SwDI versus 160.4 ± 6.6 μm2 in WT), while the number and size of melanin-concentrating hormone (MCH) immunoreactive (MCH-IR) neurons remained unchanged (cell number: 4256 ± 273.3 in Tg-SwDI versus 4494 ± 326.8 in WT. soma size: 220.1 ± 13.6 μm2 in Tg-SwDI versus 202.0 ± 7.8 μm2 in WT). The apoptotic cell death marker cleaved caspase-3 immunoreactive (Caspase-3-IR) percentage in orexin-IR neurons was significantly higher in Tg-SwDI mice than in WT controls. This selective loss of orexin-IR neurons could be associated with the abnormal sleep phenotype in these Tg-SwDI mice. Further studies are needed to determine the cause of the selective death of orexin-IR cells and relevant effects on cognition impairments in this mouse model of microvascular amyloidosis. |
| format | Article |
| id | doaj-art-215a33e3c8424f9a878a0ea1db264c6d |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-215a33e3c8424f9a878a0ea1db264c6d2025-02-04T06:32:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.15297691529769Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s diseaseYan Wu0Narayan R. Bhat1Meng Liu2Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United StatesSleep disturbances are common in Alzheimer’s disease (AD) and AD-related dementia (ADRD). We performed a sleep study on Tg-SwDI mice, a cerebral amyloid angiopathy (CAA) model, and age-matched wild-type (WT) control mice. The results showed that at 12 months of age, the hemizygous Tg-SwDI mice spent significantly more time in non-rapid eye movement (NREM) sleep (44.6 ± 2.4% in Tg-SwDI versus 35.9 ± 2.5% in WT) and had a much shorter average length of wake bout during the dark (active) phase (148.5 ± 8.7 s in the Tg-SwDI versus 203.6 ± 13.0 s in WT). Histological analysis revealed stark decreases of orexin immunoreactive (orexin-IR) neuron number and soma size in these Tg-SwDI mice (cell number: 2187 ± 97.1 in Tg-SwDI versus 3318 ± 137.9 in WT. soma size: 109.1 ± 8.1 μm2 in Tg-SwDI versus 160.4 ± 6.6 μm2 in WT), while the number and size of melanin-concentrating hormone (MCH) immunoreactive (MCH-IR) neurons remained unchanged (cell number: 4256 ± 273.3 in Tg-SwDI versus 4494 ± 326.8 in WT. soma size: 220.1 ± 13.6 μm2 in Tg-SwDI versus 202.0 ± 7.8 μm2 in WT). The apoptotic cell death marker cleaved caspase-3 immunoreactive (Caspase-3-IR) percentage in orexin-IR neurons was significantly higher in Tg-SwDI mice than in WT controls. This selective loss of orexin-IR neurons could be associated with the abnormal sleep phenotype in these Tg-SwDI mice. Further studies are needed to determine the cause of the selective death of orexin-IR cells and relevant effects on cognition impairments in this mouse model of microvascular amyloidosis.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1529769/fullsleepAlzheimer’s diseaseorexincerebral amyloid angiopathyTg-SwDIapoptosis |
| spellingShingle | Yan Wu Narayan R. Bhat Meng Liu Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease Frontiers in Aging Neuroscience sleep Alzheimer’s disease orexin cerebral amyloid angiopathy Tg-SwDI apoptosis |
| title | Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease |
| title_full | Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease |
| title_fullStr | Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease |
| title_full_unstemmed | Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease |
| title_short | Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer’s disease |
| title_sort | reduction of orexin expressing neurons and a unique sleep phenotype in the tg swdi mouse model of alzheimer s disease |
| topic | sleep Alzheimer’s disease orexin cerebral amyloid angiopathy Tg-SwDI apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1529769/full |
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