期刊
AGING CELL
卷 20, 期 12, 页码 -出版社
WILEY
DOI: 10.1111/acel.13502
关键词
Alzheimer's disease; behavioural tagging; LTP; sexual dimorphism; STDP; synaptic plasticity; synaptic tagging and capture; transcriptome profiling
资金
- Singapore Ministry of Education Academic Research Fund Tier 3 [MOE2017-T3-D1-002]
- Nanyang Technological University
- NUSMED-FOS Joint Research Programme [NUHSRO/2018/075/NUSMed-FoS/01]
Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease, but the cellular and molecular mechanisms remain unknown. Our studies on mouse models suggest that AD impacts hippocampal long-term plasticity in a sex-specific manner, with female mice showing faster decay in memory and synaptic plasticity, accompanied by neuroinflammatory markers upregulation. This disparity may contribute to the faster progression of AD in females.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据