次氯酸
神经炎症
髓过氧化物酶
双光子激发显微术
体内
小胶质细胞
海马体
疾病
荧光
生物化学
神经科学
生物物理学
物理
化学
病理
炎症
医学
免疫学
生物
生物技术
量子力学
作者
Jia Ke,Peixu Zhao,Jianfeng Li,Qiang Fu
摘要
As an inflammatory signaling molecule, hypochlorous acid (HOCl), which is generated by myeloperoxidase (MPO) catalysis, is associated with neuronal cell death during neuroinflammation and the etiology of Alzheimer's disease (AD). Thus, it is significant to employ effective tools for the in vivo mapping of HOCl during the early pathology of AD. In this study, we propose the use of an easily available two-photon fluorogenic probe, named Q-HOCl, for the specific and sensitive detection of HOCl in AD brains. The Q-HOCl probe displayed favorable selectivity and rapid response (20 s) to HOCl with a limit of detection of 12.5 nM. In addition, the Q-HOCl probe manifested splendid ability to penetrate the blood-brain barrier. Subsequently, it was utilized to visualize HOCl fluctuation induced by LPS in PC12 cells via two-photon imaging. Importantly, we monitored the elevated level of HOCl in AD brains compared to normal brains. Ultimately, based on the two-photon imaging of the hippocampus of brain slices and Morris water maze test, the cognitive ability of the AD model mice was effectually ameliorated by treatment with an MPO inhibitor. Thus, we expect that the Q-HOCl probe can be applied to reveal the capacity of HOCl in AD pathology and develop efficacious MPO inhibitor drugs for the treatment of AD.
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