Visualization of HOCl in the brains of Alzheimer's disease models using an easily available two-photon fluorogenic probe

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.

Automated summary

In this study, a two-photon fluorogenic probe named Q-HOCl was used for the specific and sensitive detection of hypochlorous acid (HOCl) in Alzheimer's disease (AD) brains. The probe showed excellent selectivity and rapid response to HOCl, with a detection limit of 12.5 nM. The elevated level of HOCl in AD brains compared to normal brains was observed, and treatment with an MPO inhibitor effectively improved the cognitive ability of AD model mice.