Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University, Philadelphia, PA, USA.
Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine Temple University, Philadelphia, PA, USA.
Mol Psychiatry. 2021 Nov;26(11):7006-7019. doi: 10.1038/s41380-019-0489-y. Epub 2019 Aug 27.
Maternal history for sporadic Alzheimer's disease (AD) predisposes the offspring to the disease later in life. However, the mechanisms behind this phenomenon are still unknown. Lifestyle and nutrition can directly modulate susceptibility to AD. Herein we investigated whether gestational high fat diet influences the offspring susceptibility to AD later in life. Triple transgenic dams were administered high fat diet or regular chow throughout 3 weeks gestation. Offspring were fed regular chow throughout their life and tested for spatial learning and memory, brain amyloidosis, tau pathology, and synaptic function. Gestational high fat diet attenuated memory decline, synaptic dysfunction, amyloid-β and tau neuropathology in the offspring by transcriptional regulation of BACE-1, CDK5, and tau gene expression via the upregulation of FOXP2 repressor. Gestational high fat diet protects offspring against the development of the AD phenotype. In utero dietary intervention could be implemented as preventative strategy against AD.
母体有散发性阿尔茨海默病（AD）病史会使后代在以后的生活中易患该病。然而，这一现象背后的机制尚不清楚。生活方式和营养可以直接调节 AD 的易感性。在此，我们研究了妊娠期高脂肪饮食是否会影响后代以后易患 AD。在整个妊娠的 3 周内，三重转基因母鼠给予高脂肪饮食或常规饮食。后代在整个生命过程中都给予常规饮食，并进行空间学习和记忆、脑淀粉样变性、tau 病理学和突触功能测试。妊娠期高脂肪饮食通过上调 FOXP2 抑制剂，调节 BACE-1、CDK5 和 tau 基因表达，从而减轻后代的记忆下降、突触功能障碍、淀粉样蛋白-β和 tau 神经病理学，进而减轻记忆下降。妊娠期高脂肪饮食可保护后代免受 AD 表型的发展。宫内饮食干预可能是预防 AD 的一种策略。
