母亲补充胆碱(MCS)可改善阿尔茨海默病(AD)模型的认知。然而,MCS对AD中神经元过度兴奋的影响尚不清楚。我们研究了MCS在建立良好的AD小鼠模型中的影响,Tg2576鼠标Tg2576小鼠中最常见的过度兴奋类型是广义EEG尖峰(发作间尖峰[IIS])。IIS在其他小鼠模型中也很常见,并发生在AD患者中。在老鼠模型中,过度兴奋性也反映在齿状回(DG)的颗粒细胞(GCs)中转录因子ΔFosB的表达升高,这是主要的细胞类型。因此,我们研究了ΔFosB在GC中的表达。我们还研究了DG的肺门神经元内的神经元标志物NeuN,因为NeuN蛋白表达减少是氧化应激或其他病理的标志。这可能很重要,因为肺门神经元调节GC兴奋性。Tg2576繁殖对接受了相对较低的饮食,中间,或者高浓度的胆碱.断奶后,所有小鼠均接受中间饮食。在喂食高胆碱饮食的小鼠的后代中,IIS频率下降,GC÷FosB表达减少,肺门NeuN表达恢复。使用新颖的对象定位任务,空间记忆得到改善。相比之下,暴露于相对低胆碱饮食的后代有几个不良影响,比如死亡率上升。它们具有最弱的肺门NeuN免疫反应性和最大的GCΔFosB蛋白表达。然而,他们的IIS频率很低,这是令人惊讶的。这些结果提供了新的证据,表明在早期生活中富含胆碱的饮食可以改善AD小鼠模型的结果。和相对较低的胆碱可以有混合的效果。这是第一项研究表明膳食胆碱可以调节兴奋过度,肺门神经元,ΔFosB,在AD动物模型中的空间记忆。
Maternal choline supplementation (MCS) improves cognition in Alzheimer\'s disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.