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