Isopropylated phenyl phosphate, an organophosphorus flame retardant, induces depressive- and anxiety-like behaviors in mice.

Isopropylated phenyl phosphate (IPP), commonly used as a flame retardant in a number of consumer products and construction materials, has been detected in human biological samples, raising concerns about human health. Limited information is currently available on the neurotoxicity of IPP. Therefore, we herein investigated the effects of IPP on emotional- and memory-related behaviors in juvenile mice. IPP (1, 10, or 100 mg/kg body weight) was orally administered to 3-week-old mice daily for two weeks. In a series of behavioral analyses, treatment with 100 mg/kg IPP induced anxiety-like behavior in the open-field test. Furthermore, treatment with 1-100 mg/kg IPP dose-dependently induced depressive-like behavior in the forced swimming test. An RNA sequencing analysis showed that 145 genes (119 up-regulated and 26 down-regulated) in the hippocampus were differentially expressed between 100 mg/kg IPP-treated mice and vehicle-treated Control mice. The representative enriched terms in the top two clusters were "ensheathment of neurons" and "myelin sheath", suggesting that IPP modified the expression of genes related to these biological processes and cellular components. Real-time PCR confirmed changes in the expression of several oligodendrocytic marker genes in these clusters. These results demonstrate that IPP may induce abnormal emotional behavior through oligodendrocyte dysfunction.