Han Xiaolei, Tang Shi, Dong Lingling, Song Lin, Dong Yi, Wang Yongxiang, Du Yifeng
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
Neurosci Lett. 2017 Mar 6;642:59-65. doi: 10.1016/j.neulet.2017.01.061. Epub 2017 Jan 27.
Alzheimer's disease (AD) is an age-related neurodegenerative brain disorder characterized by aggregation of amyloid-β (Aβ) peptide, formation of neurofibrillary tangles, synaptic loss, and neuronal cell death; however, the characteristic pathological alterations taking place in the "second brain"-enteric nervous system is still largely undefined. In this study, we aimed to detect the pathological changes in the APP/PS1 mice ileum by a novel whole mount technique. The deposition of Aβ plaque and the overexpression of phosphorylated Tau (pTau) protein were observed in the myenteric neurons of APP/PS1 mice. Compared to the control mice, the proportions of neuronal nitric oxide synthase (nNOS)+and choline acetyltransferase (ChAT)+neurons in the myenteric plexus of APP/PS1 mice significantly decreased (p<0.05). Moreover, whole mount preparations and paraffin sections both demonstrated that the number of CD68+ macrophages in the APP/PS1 mice ileum significantly increased (p<0.05). But, there was no significant difference (p>0.05) in the number of enteric HuC/D+ neurons and the density of Tuj1 between the APP/PS1 and wild type mice, which may be due to the compensatory function of enteric nervous system. These results suggest that the deposition of Aβ plaque and pTau might activate the enteric resident macrophages, further leading to the loss of myenteric nitrergic and cholinergic neurons in the enteric nervous system.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性脑疾病，其特征为β淀粉样蛋白（Aβ）肽聚集、神经原纤维缠结形成、突触丧失和神经元细胞死亡；然而，在“第二大脑”——肠神经系统中发生的特征性病理改变仍很大程度上未明确。在本研究中，我们旨在通过一种新型整装技术检测APP/PS1小鼠回肠的病理变化。在APP/PS1小鼠的肌间神经元中观察到Aβ斑块沉积和磷酸化Tau（pTau）蛋白的过表达。与对照小鼠相比，APP/PS1小鼠肌间神经丛中神经元型一氧化氮合酶（nNOS）阳性和胆碱乙酰转移酶（ChAT）阳性神经元的比例显著降低（p<0.05）。此外，整装标本和石蜡切片均显示APP/PS1小鼠回肠中CD68阳性巨噬细胞的数量显著增加（p<0.05）。但是，APP/PS1小鼠和野生型小鼠之间肠HuC/D阳性神经元的数量和Tuj1的密度没有显著差异（p>0.05），这可能是由于肠神经系统的代偿功能。这些结果表明，Aβ斑块和pTau的沉积可能激活肠内常驻巨噬细胞，进而导致肠神经系统中肌间含氮能和胆碱能神经元的丧失。
