Environmental Pollutant Formaldehyde Exposure Contributes to a Decrease in Real-Time Dopamine Concentration Dynamics in the Brain Reward Circuitry and Immunomodulating Gut Microbiome

Integrated neural signaling and gut microbiome analysis are crucial for the mechanistic understanding of environmental exposure and health. Photochemical smog is a societal challenge; formaldehyde is a component of photochemical smog and a common indoor air pollutant. Although depression-like behavior has been linked to formaldehyde exposure, the effect of exposure on real-time dopamine release remains unknown despite its significance in depression. Here, we reveal the effects of formaldehyde exposure on real-time dopamine concentration dynamics in the nucleus accumbens, elicited by electrically stimulating the medial forebrain bundle. We used fast-scan cyclic voltammetry and carbon fiber microelectrodes to quantify real-time dopamine concentration dynamics. In addition, we extracted DNA from the mice’s fecal samples and conducted 16S rRNA gene sequencing to measure the gut microbiome. We observed a decrease in real-time dopamine concentration dynamics in the nucleus accumbens associated with formaldehyde exposure, with peak dopamine concentration being 2700 ± 500 nM (no exposure), 2100 ± 400 nM (3-h exposure), and 1600 ± 500 nM (7-day exposure). By quantifying dopamine release in the nucleus accumbens evoked by electrically stimulating the medial forebrain bundle, we elucidated how formaldehyde exposure affects the associated neuronal circuitry. These experiments are the first, to the best of our knowledge, to demonstrate a significant decrease (p < 0.05) in real-time dopamine release in the nucleus accumbens following formaldehyde exposure in a duration-dependent manner. Additionally, gut microbiome analysis suggested a decrease in Lactobacillus, which has immunomodulatory functions, after 7 days of formaldehyde exposure.