A novel NIR fluorescent probe for copper(ii) imaging in Parkinson's disease mouse brain

Abstract

Abnormal copper ion (Cu²⁺) levels are considered to be one of the pathological factors of Parkinson's disease (PD), but the internal relationship between Cu²⁺ and PD progression remains elusive. Visualizing Cu²⁺ in the brain will be pivotal for comprehending the underlying pathophysiological processes of PD. In this work, a near-infrared (NIR) fluorescent probe, DDAO-Cu, capable of detecting Cu²⁺ with exceptional sensitivity (about 1.8 nM of detection limit) and selectivity, rapid response (<3 min), and deep tissue penetration, was designed for quantification and visualization of the Cu²⁺ level. It could detect not only Cu²⁺ in cells but also the changes in the Cu²⁺ level in the rotenone-induced cell and zebrafish PD models. Moreover, DDAO-Cu can cross the blood–brain barrier to image Cu²⁺ in the brain of PD model mice. The imaging result showed a significant increase in Cu²⁺ levels in brain regions of PD model mice, including the cerebral cortex, hippocampus, and striatum. Meanwhile, Cu²⁺ levels in the substantia nigra region were significantly reduced in PD model mice. It revealed the nuanced relationship of Cu²⁺ levels in different brain regions in the disease and indicated the pathological complexity of PD. Overall, DDAO-Cu represents a novel and practical tool for investigating Cu²⁺-related physiological and pathological processes underlying Parkinson's disease.