Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China; The MOE Frontier Science Center for Brain Science & Brain-machine Integration, Zhejiang University, Hangzhou, 310027, China.
School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
Biosens Bioelectron. 2022 Nov 15;216:114619. doi: 10.1016/j.bios.2022.114619. Epub 2022 Aug 7.
Olfactory dysfunction is an early symptom of neurodegenerative disease. Amyloid-beta oligomers (AβOs), the pathologic protein of Alzheimer's disease (AD), have been confirmed to be firstly deposited in olfactory bulb (OB), causing smell to malfunction. However, the detailed mechanisms underlying pathogenic nature of AβOs-induced olfactory neuronal degeneration in AD are not completely realized. Here, an early-stage olfactory dysfunction pathological model of AD in vitro based on biomimetic OB neuronal network chip was established for dynamic multi-site detection of neuronal electrical activity and network connection. We found both spike firing and correlation of overall neuronal network change regularly displayed gradually active state and then rapidly decay state after AβOs induction. Moreover, MK-801 and memantine were administrated at early-stage to detect alteration of OB neurons simulating nasal administration for AD treatment, which showed an almost recovery through the intermittent firing pattern. Together, this neuronal network-on-chip has revealed synaptic impairment and network neurodegeneration of olfactory dysfunction in AD, providing potential mechanisms information for early-stage progressive olfactory amyloidogenic pathology.
嗅觉功能障碍是神经退行性疾病的早期症状。淀粉样β寡聚体（AβOs）是阿尔茨海默病（AD）的病理蛋白，已被证实首先沉积在嗅球（OB），导致嗅觉功能障碍。然而，AβOs 诱导 AD 嗅神经元变性的致病性质的详细机制尚不完全清楚。在这里，我们建立了一种基于仿生 OB 神经元网络芯片的 AD 体外早期嗅觉功能障碍病理模型，用于神经元电活动和网络连接的动态多点检测。我们发现，AβOs 诱导后，整体神经元网络的尖峰放电和相关性均呈现出有规律的逐渐活跃状态，然后迅速衰减状态。此外，在早期给予 MK-801 和美金刚胺以模拟 AD 治疗的鼻内给药，检测 OB 神经元的变化，结果显示通过间歇性放电模式几乎完全恢复。总之，这种神经元网络芯片揭示了 AD 中嗅觉功能障碍的突触损伤和网络神经退行性变，为早期进行性淀粉样蛋白病理提供了潜在的机制信息。
