Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Ministry of Education Key Lab of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Mol Neurobiol. 2018 Jun;55(6):4928-4939. doi: 10.1007/s12035-017-0687-z. Epub 2017 Aug 3.
A majority of Alzheimer's disease (AD) cases are sporadic without known cause. People who suffered from traumatic brain injury (TBI) are more likely to develop neurodegeneration and cognitive impairments. However, the role of TBI in pathophysiology of AD remains elusive. The present study intended to explore the effect of TBI on metabolism and its role in AD pathogenesis. We subjected double transgenic AD model mice APP23/PS45 to TBI. We found that TBI promoted β-secretase cleavage of amyloid β precursor protein and amyloid β protein deposition, and exuberated the cognitive impairments in AD mouse models. H nuclear magnetic resonance (H-NMR)-based metabolomics with multivariate analysis was performed to investigate the characteristic metabolites and the related metabolic pathways in the serum and urine samples of the mice. TBI affected the metabolic patterns, methylamine metabolism, and amino acid metabolism in serum samples. Urinary metabolites showed that glycolysis and the tricarboxylic acid (TCA) cycle were perturbed. The results indicate that TBI might facilitate Alzheimer's pathogenesis by altering metabolism and inducing mitochondrial dysfunction. The study suggests that metabolite changes could also serve as biomarkers for TBI-induced neurodegeneration.
大多数阿尔茨海默病（AD）病例是散发性的，没有已知的原因。曾遭受创伤性脑损伤（TBI）的人更有可能出现神经退行性变和认知障碍。然而，TBI 在 AD 病理生理学中的作用仍不清楚。本研究旨在探讨 TBI 对代谢的影响及其在 AD 发病机制中的作用。我们使双转基因 AD 模型小鼠 APP23/PS45 遭受 TBI。我们发现 TBI 促进了淀粉样β前体蛋白的β-分泌酶裂解和淀粉样β蛋白沉积，并加剧了 AD 小鼠模型的认知障碍。通过基于 H 磁共振（H-NMR）的代谢组学和多元分析来研究小鼠血清和尿液样本中的特征代谢物和相关代谢途径。TBI 影响了血清样本中的代谢模式、甲胺代谢和氨基酸代谢。尿代谢物表明糖酵解和三羧酸（TCA）循环受到干扰。结果表明，TBI 可能通过改变代谢并诱导线粒体功能障碍促进阿尔茨海默病的发病机制。该研究表明，代谢物变化也可以作为 TBI 诱导的神经退行性变的生物标志物。
