Chronic dietary exposure to BDE-47 can induce inflammatory responses in the brain of common carp (Cyprinus carpio) and further trigger neurotoxicity through the 5-HT pathway

Polychlorinated diphenyl ethers (PBDEs) are widespread persistent organic pollutants with diverse negative effects on humans and animals. However, studies on dietary exposure to BDE-47, one of the more frequently detected PBDE congeners, and its potential to trigger neurotoxicity in animals remain relatively scarce. Thus, we investigated the effects of 42-day continuous dietary BDE-47 (40 and 4000 ng/g) exposure on inflammation and underlying neurotoxic mechanisms in Cyprinus carpio (22.10 ± 1.30 g). Integrated brain metabolomics and transcriptomics analysis revealed that BDE-47 predominantly affected the nervous system. BDE-47 up-regulated the expression of pro-inflammatory cytokines (interleukin-1β, il-1β; interleukin-8, il-8; tumor necrosis factor alpha, tnf-α) (P < 0.05) and down-regulated the expression of the anti-inflammatory cytokine interleukin-1β (il-10), accompanied by significant damage to brain tissue (P < 0.05). Specifically, BDE-47 was found to significantly reduce the levels of the neurotransmitter serotonin (5-HT) and acetylcholinesterase (AchE) (P < 0.05). Further investigations indicated that dietary BDE-47 exposure induced a remarkable decrease in the expression of factors related to the 5-HT pathway in carp, which included the serotonin receptor 5-hydroxytryptamine receptor 1D (htr1d), and three molecules in the pathway: tryptophan hydroxylase 1 (tph1), cAMP response element-binding protein (creb), and protein kinase A catalytic subunit alpha (pkaca) (P < 0.05). These findings suggested that BDE-47 induced inflammatory responses and triggered neurotoxicity by disrupting 5-HT pathway genes, resulting in neuronal contraction and glial cell proliferation. The study offered key observations into the neurotoxicity of BDE-47 in humans. These insights may contribute to the development of strategies for safeguarding human and environmental health.