Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease
Abstract Clinical evidences indicate that multifaceted gait abnormalities may manifest in Alzheimer’s disease (AD) patients, which are associated with cognitive decline. Although the correlation between hippocampal theta power and locomotion has been known for a long time, the mechanisms by how hipp...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-95585-8 |
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| author | Hong Ni Zhongzhao Guo Jie Wang Zilu Zhu Chenyi Xia Ming Xu Guohui Zhang Deheng Wang |
| author_facet | Hong Ni Zhongzhao Guo Jie Wang Zilu Zhu Chenyi Xia Ming Xu Guohui Zhang Deheng Wang |
| author_sort | Hong Ni |
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| description | Abstract Clinical evidences indicate that multifaceted gait abnormalities may manifest in Alzheimer’s disease (AD) patients, which are associated with cognitive decline. Although the correlation between hippocampal theta power and locomotion has been known for a long time, the mechanisms by how hippocampal impairment participates in the altered gait seen in AD is not fully understood. To explore the manifestations of gait disorders in AD, we characterized gait performance in 3-, 6-, and 9-month-old male 5xFAD and control mice in the semi-automated, highly sensitive, Catwalk XT system. The 5xFAD mice displayed a decrease in kinetic parameters (average speed and cadence), and spatial parameters (paw area), while the temporal parameters (stance and swing time) were significantly increased. The parameters of interlimb coordination also displayed deficits. The majority of impairment variables related to the slow speed in 5xFAD mice at 9-month-old. We further explored the theta oscillations in the brain by in vivo tetrode recording of the hippocampal CA1. The results showed that the theta oscillations reduced in the hippocampal CA1 of 5xFAD mice, which related to the gait impairments. In conclusion, gait impairments started at 6 months of age, manifested at 9 months of age in 5xFAD mice. A reduction in theta oscillation power of the hippocampal CA1 may be responsible for the gait impairments. |
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| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-8592d799bc5c4e2788d14b1c5829f65c2025-08-20T02:25:35ZengNature PortfolioScientific Reports2045-23222025-03-0115111810.1038/s41598-025-95585-8Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s diseaseHong Ni0Zhongzhao Guo1Jie Wang2Zilu Zhu3Chenyi Xia4Ming Xu5Guohui Zhang6Deheng Wang7School of Integrative Medicine, Shanghai University of Traditional Chinese MedicineSchool of Integrative Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Chinese Medicine & Integrative Medicine, Shanghai Geriatric Medical Center, Zhongshan Hospital, Fudan UniversitySchool of Integrative Medicine, Shanghai University of Traditional Chinese MedicineSchool of Integrative Medicine, Shanghai University of Traditional Chinese MedicineSchool of Integrative Medicine, Shanghai University of Traditional Chinese MedicineRehabilitation department, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineSchool of Integrative Medicine, Shanghai University of Traditional Chinese MedicineAbstract Clinical evidences indicate that multifaceted gait abnormalities may manifest in Alzheimer’s disease (AD) patients, which are associated with cognitive decline. Although the correlation between hippocampal theta power and locomotion has been known for a long time, the mechanisms by how hippocampal impairment participates in the altered gait seen in AD is not fully understood. To explore the manifestations of gait disorders in AD, we characterized gait performance in 3-, 6-, and 9-month-old male 5xFAD and control mice in the semi-automated, highly sensitive, Catwalk XT system. The 5xFAD mice displayed a decrease in kinetic parameters (average speed and cadence), and spatial parameters (paw area), while the temporal parameters (stance and swing time) were significantly increased. The parameters of interlimb coordination also displayed deficits. The majority of impairment variables related to the slow speed in 5xFAD mice at 9-month-old. We further explored the theta oscillations in the brain by in vivo tetrode recording of the hippocampal CA1. The results showed that the theta oscillations reduced in the hippocampal CA1 of 5xFAD mice, which related to the gait impairments. In conclusion, gait impairments started at 6 months of age, manifested at 9 months of age in 5xFAD mice. A reduction in theta oscillation power of the hippocampal CA1 may be responsible for the gait impairments.https://doi.org/10.1038/s41598-025-95585-8Alzheimer’s disease5xFAD mouseGaitHippocampusTheta oscillations |
| spellingShingle | Hong Ni Zhongzhao Guo Jie Wang Zilu Zhu Chenyi Xia Ming Xu Guohui Zhang Deheng Wang Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease Scientific Reports Alzheimer’s disease 5xFAD mouse Gait Hippocampus Theta oscillations |
| title | Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease |
| title_full | Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease |
| title_fullStr | Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease |
| title_full_unstemmed | Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease |
| title_short | Impairment of theta oscillations in the hippocampal CA1 region may mediate age-dependent movement alternations in the 5xFAD mouse model of Alzheimer’s disease |
| title_sort | impairment of theta oscillations in the hippocampal ca1 region may mediate age dependent movement alternations in the 5xfad mouse model of alzheimer s disease |
| topic | Alzheimer’s disease 5xFAD mouse Gait Hippocampus Theta oscillations |
| url | https://doi.org/10.1038/s41598-025-95585-8 |
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