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 (H 2 O 2 ), can interfere with the functioning of serotonergic neurons and potentially contribute to depression. Investigating the impact of H 2 O 2 on serotonergic neurons could offer valuable insights into the mechanisms underlying depression. However, there have been no effective tools for selectively imaging H 2 O 2 in these neurons so far. To address this gap, we created a small molecular fluorescent probe, PF-H2O2, designed specifically for imaging H 2 O 2 in serotonergic neurons under oxidative stress. PF-H2O2 exerts excellent serotonergic neuron-targetability and notable selectivity for H 2 O 2 . Furthermore, we discovered increased H 2 O 2 in serotonergic neurons of mice with depressive symptoms. Altogether, this endeavour unveils a pioneering tool for exploring pathophysiology linked to serotonergic neuronal dysfunction.