College of Veterinary Medicine, Southwest University, Chongqing, 402460, China.
Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, 402460, China.
Sci Rep. 2020 Dec 17;10(1):22204. doi: 10.1038/s41598-020-78903-0.
Pseudorabies virus (PRV) infection can elicit nervous system disorders. Curcumin has been reported to have neuroprotective effects. However, whether curcumin can protect neurons against PRV infection and the underlying mechanisms remain unclear. In the present study, for the first time, the protective effects of curcumin against PRV-induced oxidative stress, apoptosis, and mitochondrial dysfunction in rat hippocampal neurons and the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway were investigated. Results indicated that PRV with a titer of 3.06 × 10 TCID50 (50% tissue culture infective dose) induced oxidative damage of hippocampal neurons 2 h post-infection and that 10 μM curcumin improved the viability of PRV-infected hippocampal neurons. Blocking the BDNF/TrkB pathway reversed the neuroprotective effects of curcumin, which were imparted by decreasing the PRV-induced upregulation of nitric oxide synthase expression, repressing the PRV-activated mitochondrial apoptotic pathway, and mitochondrial dysfunction. To conclude, curcumin exhibited a neuroprotective role against PRV infection by upregulating the BDNF/TrkB pathway. This study provides insight into the anti-PRV neuroprotective application of curcumin and the underlying mechanism in the prophylaxis and treatment of neurological disorders caused by PRV infection.
伪狂犬病毒(PRV)感染可引起神经系统疾病。已有报道称姜黄素具有神经保护作用。然而,姜黄素是否能保护神经元免受 PRV 感染以及潜在的机制尚不清楚。在本研究中,首次研究了姜黄素对大鼠海马神经元 PRV 诱导的氧化应激、细胞凋亡和线粒体功能障碍以及脑源性神经营养因子(BDNF)/原肌球蛋白相关激酶 B(TrkB)通路的保护作用。结果表明,滴度为 3.06×10 TCID50(50%组织培养感染剂量)的 PRV 在感染后 2 小时诱导海马神经元的氧化损伤,而 10 μM 姜黄素可提高 PRV 感染的海马神经元的活力。阻断 BDNF/TrkB 通路可逆转姜黄素的神经保护作用,其机制是降低 PRV 诱导的一氧化氮合酶表达上调,抑制 PRV 激活的线粒体凋亡途径和线粒体功能障碍。总之,姜黄素通过上调 BDNF/TrkB 通路发挥抗 PRV 感染的神经保护作用。本研究为姜黄素在预防和治疗 PRV 感染引起的神经紊乱方面的抗 PRV 神经保护应用及其潜在机制提供了新的思路。