Kang Heeyoung, Shin Hyun Joo, An Hyeong Seok, Jin Zhen, Lee Jong Youl, Lee Jaewoong, Kim Kyung Eun, Jeong Eun Ae, Choi Kyu Yeong, McLean Catriona, Lee Kun Ho, Kim Soo Kyoung, Lee Hae Ryong, Roh Gu Seob
Department of Neurology, College of Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju 52727, Korea.
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea.
Antioxidants (Basel). 2021 Oct 21;10(11):1657. doi: 10.3390/antiox10111657.
Lipocalin-2 (LCN2) is an inflammatory protein with diverse functions in the brain. Although many studies have investigated the mechanism of LCN2 in brain injuries, the effect of LCN2 on amyloid-toxicity-related memory deficits in a mouse model of Alzheimer's disease (AD) has been less studied. We investigated the role of LCN2 in human AD patients using a mouse model of AD. We created an AD mouse model by injecting amyloid-beta oligomer (AβO) into the hippocampus. In this model, animals exhibited impaired learning and memory. We found LCN2 upregulation in the human brain frontal lobe, as well as a positive correlation between white matter ischemic changes and serum LCN2. We also found increased astrocytic LCN2, microglia activation, iron accumulation, and blood-brain barrier disruption in AβO-treated hippocampi. These findings suggest that LCN2 is involved in a variety of amyloid toxicity mechanisms, especially neuroinflammation and oxidative stress.
脂质运载蛋白-2（LCN2）是一种在大脑中具有多种功能的炎症蛋白。尽管许多研究已经探究了LCN2在脑损伤中的作用机制，但LCN2对阿尔茨海默病（AD）小鼠模型中与淀粉样蛋白毒性相关的记忆缺陷的影响却鲜有研究。我们使用AD小鼠模型研究了LCN2在人类AD患者中的作用。我们通过向海马体注射淀粉样β寡聚体（AβO）创建了一个AD小鼠模型。在这个模型中，动物表现出学习和记忆受损。我们发现人类大脑额叶中LCN2上调，以及白质缺血性改变与血清LCN2之间存在正相关。我们还发现在经AβO处理的海马体中，星形胶质细胞LCN2增加、小胶质细胞激活、铁积累和血脑屏障破坏。这些发现表明LCN2参与了多种淀粉样蛋白毒性机制，尤其是神经炎症和氧化应激。
