Chronic Pb Exposure Induces Anxiety and Depression-like Behaviors in Mice via Excitatory Neuronal Hyperexcitability in Ventral Hippocampal Dentate Gyrus

Lead (Pb) is a widespread neurotoxic pollutant. Pb exposureisassociated with mood disorders, with no well-established neural mechanismselucidated. In the present study, we aimed to investigate whetherexcitatory neurons in the dentate gyrus subregion of the ventral hippocampus(vDG) played a key role in Pb-induced anxiety and depression-likebehaviors. C57BL/6 mice were exposed to 100 ppm Pb starting on day1 of pregnancy until experiments were performed using the offspring.Behavioral studies suggested that chronic Pb exposure triggered anxietyand depression-like behaviors. A combination of electrophysiological,optogenetic, and immunohistochemistry experiments was conducted. Resultsshowed that Pb exposure resulted in excitatory neuronal hyperexcitabilityin vDG and that the behavioral deficits caused by Pb exposure couldbe rescued by inhibition of excitatory neuronal activity. Moreover,it was found that the action potential (AP) threshold of excitatoryneurons was decreased by electrophysiological recordings. Our studydemonstrates a significant role for excitatory neurons in vDG in Pb-inducedanxiety and depression-like behaviors in mice, which is likely a resultof decreased AP threshold. These outcomes can serve as an importantbasis for understanding mechanisms of anxiety and depression underenvironmental Pb exposure and help in the design of therapeutic strategies. Pb is widespread and notable for itsneurotoxic effectseven at low levels of exposure encountered in the general environment.This study provides previously unexplored avenues of investigationfor the development of potential therapeutic targets in the treatmentof anxiety and depression due to environmental Pb exposure.

Automated summary

This study found that lead exposure can lead to anxiety and depression-like behaviors, and excitatory neurons play a key role in this phenomenon. Through a series of experiments, the results showed that lead exposure can result in excitatory neuronal hyperexcitability, and the behavioral deficits caused by lead exposure were alleviated by inhibiting excitatory neuronal activity. The study demonstrates the significant role of excitatory neurons in lead-induced anxiety and depression-like behaviors under environmental exposure.