A versatile fluorescent probe for hydrogen peroxide in serotonergic neurons of living brains of mice with depression†

Depression, a prevalent mental illness, is intricately linked with the neurotransmitters in the brain, while serotonin as a crucial regulator of mood, energy levels, and memory, has been implicated in depression. So, the release of serotonin by serotonergic neurons plays a significant role in the development of depression. Notably, the foremost marker of oxidative stress, hydrogen peroxide (H₂O₂), can interfere with the functioning of serotonergic neurons and potentially contribute to depression. Investigating the impact of H₂O₂ on serotonergic neurons could offer valuable insights into the mechanisms underlying depression. However, there have been no effective tools for selectively imaging H₂O₂ in these neurons so far. To address this gap, we created a small molecular fluorescent probe, PF-H₂O₂, designed specifically for imaging H₂O₂ in serotonergic neurons under oxidative stress. PF-H₂O₂ exerts excellent serotonergic neuron-targetability and notable selectivity for H₂O₂. Furthermore, we discovered increased H₂O₂ in serotonergic neurons of mice with depressive symptoms. Altogether, this endeavour unveils a pioneering tool for exploring pathophysiology linked to serotonergic neuronal dysfunction.