Shen Jinghua, Gao Lu, Gao Jingjing, Wang Licong, Yan Dongying, Wang Ying, Meng Jia, Li Hong, Chen Dawei, Wu Jie
Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, Jinzhou 121001, China.
School of Public Health, Jinzhou Medical University, Jinzhou 121001, China.
Biomolecules. 2025 Jul 27;15(8):1087. doi: 10.3390/biom15081087.
Developmental exposure to polybrominated diphenyl ethers (PBDEs), which are commonly used as flame retardants, results in irreversible cognitive impairments. Postnatal hippocampal neurogenesis, which occurs in the subgranular zone (SGZ) of the dentate gyrus, is critical for neuronal circuits and plasticity. Wnt7a-Frizzled5 (FZD5) is essential for both neurogenesis and synapse formation; moreover, Wnt signaling participates in PBDE neurotoxicity and also contributes to the neuroprotective effects of melatonin. Therefore, we investigated the impacts of perinatal decabromodiphenyl ether (BDE-209) exposure on hippocampal neurogenesis and synaptogenesis in juvenile rats through BrdU injection and Golgi staining, as well as the alleviation of melatonin pretreatment. Additionally, we identified the structural basis of Wnt7a and two compounds via molecular docking. The hippocampal neural progenitor pool (Sox2+BrdU+ and Sox2+GFAP+cells), immature neurons (DCX+) differentiated from neuroblasts, and the survival of mature neurons (NeuN+) in the dentate gyrus were inhibited. Moreover, in BDE-209-exposed offspring rats, it was observed that dendritic branching and spine density were reduced, alongside the long-lasting suppression of the Wnt7a-FZD5/β-catenin pathway and targeted genes (, , , , and ) expression. Melatonin alleviated BDE-209-disrupted memory, along with hippocampal neurogenesis and dendritogenesis, for which the restoration of Wnt7a-FZD5 signaling may be beneficial. This study suggested that melatonin could represent a potential intervention for the cognitive deficits induced by PBDEs.
多溴二苯醚（PBDEs）常用作阻燃剂，发育过程中暴露于该物质会导致不可逆的认知障碍。出生后海马神经发生发生在齿状回的颗粒下区（SGZ），对神经回路和可塑性至关重要。Wnt7a - 卷曲蛋白5（FZD5）对神经发生和突触形成均必不可少；此外，Wnt信号传导参与PBDE的神经毒性作用，同时也有助于褪黑素的神经保护作用。因此，我们通过注射BrdU和高尔基染色研究了围产期十溴二苯醚（BDE - 209）暴露对幼鼠海马神经发生和突触形成的影响，以及褪黑素预处理的缓解作用。此外，我们通过分子对接确定了Wnt7a和两种化合物的结构基础。齿状回中的海马神经祖细胞池（Sox2 + BrdU +和Sox2 + GFAP +细胞）、从神经母细胞分化而来的未成熟神经元（DCX +）以及成熟神经元（NeuN +）的存活均受到抑制。此外，在暴露于BDE - 209的后代大鼠中，观察到树突分支和棘密度降低，同时Wnt7a - FZD5/β - 连环蛋白通路和靶向基因（、、、和）的表达受到长期抑制。褪黑素缓解了BDE - 209破坏的记忆以及海马神经发生和树突形成，恢复Wnt7a - FZD5信号传导可能对此有益。这项研究表明，褪黑素可能是一种针对PBDEs诱导的认知缺陷的潜在干预措施。
