NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Neurosci Lett. 2022 Feb 6;771:136423. doi: 10.1016/j.neulet.2021.136423. Epub 2021 Dec 26.
Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein encoded by SERPINF1 and our previous study reported that PEDF may have antidepressant effects. As a key brain region regulating cognition, memory and emotion, the prefrontal cortex (PFC) has been studied extensively in major depressive disorder (MDD), but there are few reports on the relationship between PEDF and the PFC. In this study, enzyme-linked immunosorbent assay showed that the PEDF level was decreased in the plasma of MDD patients compared with that of healthy controls. Western blotting validated that the PEDF expression in the PFC was downregulated in the mouse chronic social defeat stress and rat chronic unpredictable mild stress models of depression. Correspondingly, normal mice overexpressing PEDF in the PFC showed depression-resistant phenotypes. We detected PFC metabolite levels by liquid chromatography-tandem mass spectrometry and found significant upregulation of 5-hydroxyindoleacetic acid, kynurenine, 5-hydroxytryptamine, ornithine and glutamine, and downregulation of 5-hydroxytryptophan, glutamic acid and aspartic acid in PEDF-overexpressing mice compared with control mice, in which no such changes were detected. Combined with the above findings, this provides an insight into a potential mechanism of the antidepressant effects of PEDF via the PFC, which may help to improve understanding of depression pathophysiology.
色素上皮衍生因子（PEDF）是一种多功能糖蛋白，由 SERPINF1 编码，我们之前的研究报道 PEDF 可能具有抗抑郁作用。前额叶皮层（PFC）作为调节认知、记忆和情绪的关键脑区，在重度抑郁症（MDD）中得到了广泛研究，但关于 PEDF 与 PFC 之间的关系的报道较少。在这项研究中，酶联免疫吸附试验显示，与健康对照组相比，MDD 患者的血浆 PEDF 水平降低。Western blot 验证了在慢性社交挫败应激和慢性不可预测轻度应激抑郁模型的小鼠中 PFC 中 PEDF 的表达下调。相应地，在 PFC 中过表达 PEDF 的正常小鼠表现出抗抑郁表型。我们通过液相色谱-串联质谱法检测了 PFC 代谢物水平，发现 PEDF 过表达小鼠的 5-羟色胺酸、犬尿氨酸、5-羟色胺、鸟氨酸和谷氨酰胺水平显著上调，而 5-羟色氨酸、谷氨酸和天冬氨酸水平下调，而在对照小鼠中则未检测到这些变化。结合上述发现，这为 PEDF 通过 PFC 发挥抗抑郁作用的潜在机制提供了一个深入的了解，这可能有助于提高对抑郁病理生理学的理解。
