Illuminating the Function of the Hydroxyl Radical in the Brains of Mice with Depression Phenotypes by Two-Photon Fluorescence Imaging

Abstract

Depression is intimately linked with oxidative stress. As one of the most reactive and oxidative reactive oxygen species that is overproduced during oxidative stress, the hydroxyl radical (^. OH) can cause macromolecular damage and subsequent neurological diseases. However, due to the high reactivity and low concentration of ^. OH, precise exploration of ^. OH in brains remains a challenge. The two-photon fluorescence probe MD-B was developed for in situ ^. OH imaging in living systems. This probe achieves exceptional selectivity towards ^. OH through the one-electron oxidation of 3-methyl-pyrazolone as a new specific recognition site. MD-B can be used to map ^. OH in mouse brain, thereby revealing that increased ^. OH is positively correlated with the severity of depression phenotypes. Furthermore, ^. OH has been shown to inactivate deacetylase SIRT1, thereby leading to the occurrence and development of depression phenotypes. This work provides a new strategy for the future treatment of depression.

Keywords: depression; fluorescence imaging; fluorogenic probes; hydroxyl radicals; oxidative stress.