Perfluorooctanoic acid (PFOA), a hazardous environmental pollutant, has been found to enhance hepatic synthesis of fibroblast growth factor 21 (FGF21). FGF21 can enter the brain and increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were orally administered PFOA to evaluate how it regulates emotion. Exposure of mice to PFOA (1 mg kg-1 bw) for 10 consecutive days (PFOA-mice) caused anxiety-like behaviors and a peroxisome proliferator-activated receptor α (PPARα)-dependent increase in hepatic FGF21 synthesis. The levels of CRF expression in not only PVN but also basolateral amygdala complex (BLA) neurons of PFOA-mice were increased via FGF receptor 1 (FGF-R1) activation. However, the microinjection of FGF-R1 or CRF 1 receptor (CRF-R1) antagonist in the BLA rather than the PVN of PFOA-mice could relieve their anxiety-like behaviors. In addition, external capsule-BLA synaptic transmission in PFOA-mice was enhanced by increasing CRF-R1-mediated presynaptic glutamate release, which was corrected by the blockade of PPARα, FGF-R1 and CRF-R1 or the inhibition of PKA. Furthermore, the threshold of frequency-dependent long-term potentiation (LTP) induction was decreased in the BLA of PFOA-mice, which depended on the activation of PPARα, FGF-R1, CRF-R1, PKA and NMDA receptor (NMDAR), whereas long-term depression (LTD) induction was unchanged. Thus, the results indicate that the exposure of male mice to PFOA (1 mg kg-1 bw) enhances CRF expression in BLA neurons by increasing hepatic FGF21 synthesis, which then enhances CRF-R1-mediated presynaptic glutamate release to facilitate NMDAR-dependent BLA-LTP induction, leading to the production of anxiety-like behaviors.

全氟辛酸 (PFOA) 是一种有害的环境污染物，已被发现可增强成纤维细胞生长因子 21 (FGF21) 的肝脏合成。FGF21可以进入大脑并增加室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）的表达。在这项研究中，成年雄性小鼠口服全氟辛酸，以评估它如何调节情绪。小鼠连续 10 天接触全氟辛酸（1 mg kg-1 bw）（全氟辛酸小鼠）会导致类似焦虑的行为和过氧化物酶体增殖物激活受体 α（PPARα）依赖性的肝脏 FGF21 合成增加。PFOA 小鼠不仅 PVN，而且基底外侧杏仁核复合体 (BLA) 神经元中的 CRF 表达水平通过以下方式增加：FGF 受体 1 (FGF-R1) 激活。然而，在 BLA 而非 PFOA 小鼠的 PVN 中显微注射 FGF-R1 或 CRF 1 受体（CRF-R1）拮抗剂可以缓解它们的焦虑样行为。此外，通过增加 CRF-R1 介导的突触前谷氨酸释放来增强 PFOA 小鼠的外囊-BLA 突触传递，这通过阻断 PPARα、FGF-R1 和 CRF-R1 或抑制 PKA 得到纠正。此外，PFOA 小鼠 BLA 的频率依赖性长时程增强 (LTP) 诱导阈值降低，这取决于 PPARα、FGF-R1、CRF-R1、PKA 和 NMDA 受体 (NMDAR) 的激活，而长期抑郁 (LTD) 诱导没有变化。因此，