Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Laboratory of Brain Disorders (Ministry of Science and Technology), Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
Department of Anatomy, Capital Medical University, Beijing, China.
Mediators Inflamm. 2019 May 15;2019:7898095. doi: 10.1155/2019/7898095. eCollection 2019.
Accumulated evidences show that neuroinflammation play a pivotal role in the pathogenesis of depression. Neuropeptide Y (NPY) and its receptors have been demonstrated to have anti-inflammative as well as antidepressant effects. In the present study, the ability of NPY to modulate depressive-like behaviors induced by lipopolysaccharides (LPS) in rats and the receptors and signaling mechanisms involved were investigated. Continuous injection LPS (i.p) for 4 days led to development of depressive-like behaviors in rats, accompanied with M1-type microglia activation and increased levels of IL-1 as well as decreased levels of NPY and Y2R expression in the mPFC selectively. Local injection of NPY into the medial prefrontal cortex (mPFC) ameliorated the depression-like behaviors and suppressed the NLRP3 inflammasome signaling pathway. Y2R agonist PYY (3-36) mimicked and Y2R antagonist BIIE0246 abolished the NPY effects in the mPFC. All these results suggest that NPY and Y2R in the mPFC are involved in the pathophysiology of depression and NPY plays an antidepressant role in the mPFC mainly via Y2R, which suppresses the NLRP3 signaling pathway, in LPS-induced depression model rats.
积累的证据表明，神经炎症在抑郁症的发病机制中起着关键作用。神经肽 Y（NPY）及其受体已被证明具有抗炎和抗抑郁作用。在本研究中，研究了 NPY 调节脂多糖（LPS）诱导的大鼠抑郁样行为的能力以及涉及的受体和信号机制。连续腹腔注射 LPS（i.p）4 天可导致大鼠出现抑郁样行为，伴有 M1 型小胶质细胞激活，以及 mPFC 中 IL-1 水平升高和 NPY 及 Y2R 表达水平降低。NPY 局部注射到前额叶皮质（mPFC）可改善抑郁样行为，并抑制 NLRP3 炎症小体信号通路。Y2R 激动剂 PYY（3-36）模拟了 NPY 的作用，而 Y2R 拮抗剂 BIIE0246 则消除了 NPY 在 mPFC 中的作用。这些结果表明，mPFC 中的 NPY 和 Y2R 参与了抑郁症的病理生理学，NPY 主要通过 Y2R 在 mPFC 中发挥抗抑郁作用，抑制 LPS 诱导的抑郁模型大鼠中的 NLRP3 信号通路。
