Seo Hyeon Jeong, Park Jung Eun, Choi Seong-Min, Kim Taekyoung, Cho Soo Hyun, Lee Kyung-Hwa, Song Woo Keun, Song Juhyun, Jeong Han-Seong, Kim Dong Hyun, Kim Byeong C
Department of Biomedical Sciences, Graduate School, Chonnam National University, 61186 Gwangju, Korea.
Department of Biomedical Science, College of Natural Sciences, Chosun University, 61452 Gwangju, Korea.
Int J Mol Sci. 2021 Jan 12;22(2):698. doi: 10.3390/ijms22020698.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a rapid accumulation of amyloid β (Aβ) protein in the hippocampus, which impairs synaptic structures and neuronal signal transmission, induces neuronal loss, and diminishes memory and cognitive functions. The present study investigated the impact of neuregulin 1 (NRG1)-ErbB4 signaling on the impairment of neural networks underlying hippocampal long-term potentiation (LTP) in 5xFAD mice, a model of AD with greater symptom severity than that of TG2576 mice. Specifically, we observed parvalbumin (PV)-containing hippocampal interneurons, the effect of NRG1 on hippocampal LTP, and the functioning of learning and memory. We found a significant decrease in the number of PV interneurons in 11-month-old 5xFAD mice. Moreover, synaptic transmission in the 5xFAD mice decreased at 6 months of age. The 11-month-old transgenic AD mice showed fewer inhibitory PV neurons and impaired NRG1-ErbB4 signaling than did wild-type mice, indicating that the former exhibit the impairment of neuronal networks underlying LTP in the hippocampal Schaffer-collateral pathway. In conclusion, this study confirmed the impaired LTP in 5xFAD mice and its association with aberrant NRG1-ErbB signaling in the neuronal network.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是淀粉样β（Aβ）蛋白在海马体中快速积累，这会损害突触结构和神经元信号传递，导致神经元丢失，并削弱记忆和认知功能。本研究调查了神经调节蛋白1（NRG1）-表皮生长因子受体4（ErbB4）信号传导对5xFAD小鼠海马体长期增强（LTP）潜在神经网络损伤的影响，5xFAD小鼠是一种比TG2576小鼠症状更严重的AD模型。具体而言，我们观察了含小白蛋白（PV）的海马中间神经元、NRG1对海马LTP的影响以及学习和记忆功能。我们发现11月龄5xFAD小鼠中PV中间神经元数量显著减少。此外，5xFAD小鼠在6月龄时突触传递减少。与野生型小鼠相比，11月龄转基因AD小鼠中抑制性PV神经元更少，NRG1-ErbB4信号传导受损，这表明前者在海马体谢弗侧支通路中表现出LTP潜在神经网络的损伤。总之，本研究证实了5xFAD小鼠中LTP受损及其与神经网络中异常NRG1-ErbB信号传导的关联。
