Melatonin improves synaptic morphological plasticity of adolescent male rats after perinatal BDE-209 exposure via SIRT1-mediated LIMK1 and CREB signaling

Brominated flame retardants polybrominated diphenyl ethers (PBDEs) have posed threat to ecosystems and human health, especially on neurodevelopment, while the mechanisms remain obscure. Here, we assessed recognition memory for new object and spontaneous behavior of adolescent male rats after perinatal BDE-209 exposure. Considering that the miR-34 family is linked to spines morphology and memory formation and mediates neuroprotective role of melatonin through Sirtuin1 (SIRT1), we investigated the role of miR-34 in developmental neurotoxicity of BDE-209 of rats with or without melatonin pretreatment. We analyzed dendritic arborisation and spines density of pyramidal neurons in both prefrontal cortex (PFC) and hippocampal CA1 region via Golgi-staining and Sholl tools; then conducted miRNA sequencing and verified differentially expressed miRNAs and their targets. Our findings indicated that miR-34c and miR-134 were significantly up-regulated in the hippocampus and PFC of maternal BDE-209-exposed rats, as a target of miR-34c simultaneously upstream regulator for miR-134, neuronal SIRT1 level was decreased correspondingly. Furthermore, miR-134 targeted LIMK1/cofilin and CREB/BDNF pathway contributing to changes in dendritic morphology. Melatonin pretreatment restored synaptic morphological plasticity especially spines density in hippocampal and cortical neurons, partially through elevating SIRT1 expression, and alleviated BDE-209-caused memory deficits, providing a potential neuroprotective intervention.