Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease
Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event an...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/153998 |
| _version_ | 1811693377865908224 |
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| author | Navakkode, Sheeja Gaunt, Jessica Ruth Pavon, Maria Vazquez Bansal, Vibhavari Aysha Abraham, Riya Prasad Chong, Yee Song Ch'ng, Toh Hean Sajikumar, Sreedharan |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Navakkode, Sheeja Gaunt, Jessica Ruth Pavon, Maria Vazquez Bansal, Vibhavari Aysha Abraham, Riya Prasad Chong, Yee Song Ch'ng, Toh Hean Sajikumar, Sreedharan |
| author_sort | Navakkode, Sheeja |
| collection | NTU |
| description | Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event and appears before significant accumulation of amyloid plaques and neuronal degeneration. However, it is unclear whether sexual dimorphism at the synaptic level contributes to the higher risk and prevalence of AD in females. Our studies on APP/PS1 (APPSwe/PS1dE9) mouse model show that AD impacts hippocampal long-term plasticity in a sex-specific manner. Long-term potentiation (LTP) induced by strong tetanic stimulation (STET), theta burst stimulation (TBS) and population spike timing-dependent plasticity (pSTDP) show a faster decay in AD females compared with age-matched AD males. In addition, behavioural tagging (BT), a model of associative memory, is specifically impaired in AD females with a faster decay in memory compared with males. Together with the plasticity and behavioural data, we also observed an upregulation of neuroinflammatory markers, along with downregulation of transcripts that regulate cellular processes associated with synaptic plasticity and memory in females. Immunohistochemistry of AD brains confirms that female APP/PS1 mice carry a higher amyloid plaque burden and have enhanced microglial activation compared with male APP/PS1 mice. Their presence in the diseased mice also suggests a link between the impairment of LTP and the upregulation of the inflammatory response. Overall, our data show that synaptic plasticity and associative memory impairments are more prominent in females and this might account for the faster progression of AD in females. |
| first_indexed | 2024-10-01T06:50:43Z |
| format | Journal Article |
| id | ntu-10356/153998 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:50:43Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1539982023-02-28T17:10:33Z Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease Navakkode, Sheeja Gaunt, Jessica Ruth Pavon, Maria Vazquez Bansal, Vibhavari Aysha Abraham, Riya Prasad Chong, Yee Song Ch'ng, Toh Hean Sajikumar, Sreedharan Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences National University of Singapore Science::Medicine Alzheimer's Disease Behavioural Tagging Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event and appears before significant accumulation of amyloid plaques and neuronal degeneration. However, it is unclear whether sexual dimorphism at the synaptic level contributes to the higher risk and prevalence of AD in females. Our studies on APP/PS1 (APPSwe/PS1dE9) mouse model show that AD impacts hippocampal long-term plasticity in a sex-specific manner. Long-term potentiation (LTP) induced by strong tetanic stimulation (STET), theta burst stimulation (TBS) and population spike timing-dependent plasticity (pSTDP) show a faster decay in AD females compared with age-matched AD males. In addition, behavioural tagging (BT), a model of associative memory, is specifically impaired in AD females with a faster decay in memory compared with males. Together with the plasticity and behavioural data, we also observed an upregulation of neuroinflammatory markers, along with downregulation of transcripts that regulate cellular processes associated with synaptic plasticity and memory in females. Immunohistochemistry of AD brains confirms that female APP/PS1 mice carry a higher amyloid plaque burden and have enhanced microglial activation compared with male APP/PS1 mice. Their presence in the diseased mice also suggests a link between the impairment of LTP and the upregulation of the inflammatory response. Overall, our data show that synaptic plasticity and associative memory impairments are more prominent in females and this might account for the faster progression of AD in females. Ministry of Education (MOE) Nanyang Technological University Published version This research is supported by Singapore Ministry of Education Academic Research Fund Tier 3 (MOE2017-T3-1-002; THC and SS) and by Nanyang Assistant Professorship (NAP) from Nanyang Technological University, Singapore. A part of this work was also supported by NUSMED-FOS Joint Research Programme (NUHSRO/2018/075/NUSMed-FoS/01) to S.S. 2022-06-07T02:16:04Z 2022-06-07T02:16:04Z 2021 Journal Article Navakkode, S., Gaunt, J. R., Pavon, M. V., Bansal, V. A., Abraham, R. P., Chong, Y. S., Ch'ng, T. H. & Sajikumar, S. (2021). Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease. Aging Cell, 20(12), e13502-. https://dx.doi.org/10.1111/acel.13502 1474-9718 https://hdl.handle.net/10356/153998 10.1111/acel.13502 34796608 2-s2.0-85119286594 12 20 e13502 en MOE2017-T3-D1-002 NUHSRO/2018/075/NUSMed-FoS/01 Aging Cell © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Science::Medicine Alzheimer's Disease Behavioural Tagging Navakkode, Sheeja Gaunt, Jessica Ruth Pavon, Maria Vazquez Bansal, Vibhavari Aysha Abraham, Riya Prasad Chong, Yee Song Ch'ng, Toh Hean Sajikumar, Sreedharan Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title | Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title_full | Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title_fullStr | Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title_full_unstemmed | Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title_short | Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease |
| title_sort | sex specific accelerated decay in time activity dependent plasticity and associative memory in an animal model of alzheimer s disease |
| topic | Science::Medicine Alzheimer's Disease Behavioural Tagging |
| url | https://hdl.handle.net/10356/153998 |
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