Ryu J, Hong B-H, Kim Y-J, Yang E-J, Choi M, Kim H, Ahn S, Baik T-K, Woo R-S, Kim H-S
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Republic of Korea.
Cell Death Dis. 2016 Feb 25;7(2):e2117. doi: 10.1038/cddis.2016.30.
The neuregulin (NRG) family of epidermal growth factor-related proteins is composed of a wide variety of soluble and membrane-bound proteins that exert their effects via the tyrosine kinase receptors ErbB2-ErbB4. In the nervous system, the functions of NRG1 are essential for peripheral myelination, the establishment and maintenance of neuromuscular and sensorimotor systems and the plasticity of cortical neuronal circuits. In the present study, we report that an intracerebroventricular infusion of NRG1 attenuated cognitive impairments in 13-month-old Tg2576 mice, an animal model of Alzheimer's disease (AD). In addition, according to Golgi-Cox staining, NRG1 rescued the reduction in the number of dendritic spines detected in the brains of Tg2576 mice compared with vehicle (PBS)-infused mice. This result was also corroborated in vitro as NRG1 attenuated the oligomeric amyloid beta peptide(1-42) (Aβ(1-42))-induced decrease in dendritic spine density in rat primary hippocampal neuron cultures. NRG1 also alleviated the decrease in neural differentiation induced by oligomeric Aβ(1-42) in mouse fetal neural stem cells. Collectively, these results suggest that NRG1 has a therapeutic potential for AD by alleviating the reductions in dendritic spine density and neurogenesis found in AD brains.
神经调节蛋白（NRG）家族的表皮生长因子相关蛋白由多种可溶性和膜结合蛋白组成，它们通过酪氨酸激酶受体ErbB2 - ErbB4发挥作用。在神经系统中，NRG1的功能对于外周髓鞘形成、神经肌肉和感觉运动系统的建立与维持以及皮质神经元回路的可塑性至关重要。在本研究中，我们报告脑室内注入NRG1可减轻13月龄Tg2576小鼠（一种阿尔茨海默病（AD）动物模型）的认知障碍。此外，根据高尔基-考克斯染色，与注入溶剂（磷酸盐缓冲液）的小鼠相比，NRG1挽救了Tg2576小鼠大脑中检测到的树突棘数量的减少。在体外实验中也证实了这一结果，因为NRG1减弱了寡聚淀粉样β肽（1 - 42）（Aβ（1 - 42））诱导的大鼠原代海马神经元培养物中树突棘密度的降低。NRG1还减轻了寡聚Aβ（1 - 42）在小鼠胎儿神经干细胞中诱导的神经分化的减少。总体而言，这些结果表明NRG1通过减轻AD大脑中发现的树突棘密度和神经发生的降低，对AD具有治疗潜力。
