Wang Ya, Chen Yuning, Chen Houlin, Samsom James N, Shu Minfei, Gao Xuehui, Li Qiyu, Chen Kangmin, Wang Le, Liu Fang
Institute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.
Environ Int. 2025 Aug;202:109631. doi: 10.1016/j.envint.2025.109631. Epub 2025 Jun 23.
Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems related to mood disorders. PFOA exposure (5 mg/kg) for 10 consecutive days caused depression-like behaviors in male mice. We measured increased corticosterone in serum and in the hippocampus of PFOA-exposed mice, which were linked to enhanced CRF expression measured in the PVN. Elevated corticosterone was associated with reductions in glucocorticoid receptor (GR) protein expression within the hippocampus. CRFR1 antagonist injected into the PVN and intracerebroventricular (i.c.v.) GR antagonist both reduced depression-like behaviors, respectively. In addition, NMDA-dependent Schaeffer collateral-CA3 synaptic transmission in PFOA-exposed mice was disrupted. Synaptic deficits could be corrected by either CRFR1 or GR antagonists. In summary, we found exposure of male mice to PFOA enhances CRF expression, which then activates the HPA axis to disrupt GR expression in the hippocampus, leading to depression-like behaviors. This data is relevant for understanding the potential harmful health effects of PFOA.
全氟辛酸（PFOA）是一种环境内分泌干扰物，已被发现可增加室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）的表达。在本研究中，对成年雄性小鼠进行经口灌胃（p.o.）给予PFOA，以评估其是否会扰乱与情绪障碍相关的系统。连续10天暴露于PFOA（5毫克/千克）会导致雄性小鼠出现抑郁样行为。我们检测到暴露于PFOA的小鼠血清和海马中的皮质酮增加，这与PVN中检测到的CRF表达增强有关。皮质酮升高与海马内糖皮质激素受体（GR）蛋白表达降低有关。向PVN注射CRFR1拮抗剂和脑室内（i.c.v.）注射GR拮抗剂均分别减少了抑郁样行为。此外，暴露于PFOA的小鼠中依赖N-甲基-D-天冬氨酸（NMDA）的舍费尔侧支-海马CA3突触传递受到破坏。CRFR1或GR拮抗剂均可纠正突触缺陷。总之，我们发现雄性小鼠暴露于PFOA会增强CRF表达，进而激活下丘脑-垂体-肾上腺（HPA）轴，破坏海马中的GR表达，导致抑郁样行为。该数据对于理解PFOA对健康的潜在有害影响具有重要意义。
