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- W4312086675 abstract "Background Alzheimer’s disease (AD) patients exhibit early symptoms of non-rapid eye movement sleep (NREM) reduction and relatively REM sleep increase, which influences homeostatic synaptic plasticity (HSP) in cortical and subcortical neurons. Meanwhile, β-amyloid peptides can suppress synaptic plasticity in hippocampus to impair learning/memory in animal studies. Method In accordance with IACUC of Vanderbilt University Medical center, coronal brain slices were prepared from wt and hemi 5xFAD mice at postnatal days (P)30, 60-90 and 120-150. Whole-cell patch-clamp recordings were made from hippocampal CA1 pyramidal neurons to record spontaneous excitatory synaptic currents (sEPSCs) at 32°C (clamped at -55.8mV, chloride reversal potentials). Slow-wave oscillations (SWOs, 0.5 Hz, 10 min) were induced by injecting sinusoidal currents into neurons to simulate neuronal activity (up/down state) during NREM sleep. 200 µM β-amyloid peptides were used in ACSF for this study. Result Compared with age-matched wt littermates at P30 and P60-90, sEPSCs in hippocampal neurons from hemi 5xFAD mice (n = 4 mice) exhibited larger amplitudes and higher frequency. However, at P120-150, sEPSCs in neurons from hemi 5xFAD mice (n = 5 mice) became smaller than wt littermates (n = 4 mice), suggesting that excitatory synapses in hemi 5xFAD mice may be altered along the ageing course. Moreover, following SWO induction, HSP could be induced in neurons from wt littermates at all postnatal ages (n = 5 mice) and post-SWO sEPSCs in neurons were increased. However, HSP could not be induced in neurons from hemi 5xFAD mice at P120-150, except P30 and P60-90. Moreover, 200 µM β-amyloid peptides can suppress this synaptic potentiation in neurons from hemi 5XFAD mice at P90 (n = 4 mice). Conclusion Reduced NREM sleep activity in hemi 5xFAD mice can impair sEPSCs and HSP in hippocampal CA1 neurons along the ageing course, and subclinical β-amyloid peptides can suppress this sleep-related homeostatic synaptic potentiation, which contributes to cognitive deficits in AD patients." @default.
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- W4312086675 date "2022-12-01" @default.
- W4312086675 modified "2023-09-27" @default.
- W4312086675 title "Subclinical β‐amyloid peptides impair homeostatic synaptic potentiation in hippocampal neurons in 5XFAD mice" @default.
- W4312086675 doi "https://doi.org/10.1002/alz.066138" @default.
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