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Title: Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease
Authors: Navakkode, Sheeja
Gaunt, Jessica Ruth
Pavon, Maria Vazquez
Bansal, Vibhavari Aysha
Abraham, Riya Prasad
Chong, Yee Song
Ch'ng, Toh Hean
Sajikumar, Sreedharan
Keywords: Science::Medicine
Issue Date: 2021
Source: 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-.
Project: MOE2017-T3-D1-002
Journal: Aging Cell
Abstract: 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.
ISSN: 1474-9718
DOI: 10.1111/acel.13502
Rights: © 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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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