Department of Neurology, The 960(th) Hospital of Joint Logistics Support, PLA, Jinan 250031, PR China; Department of Human Anatomy, Histology and Embryology, The Fourth Military Medical University, Xi'an 710032, PR China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Jinan 250021, PR China.
Neurosci Lett. 2022 Sep 25;788:136851. doi: 10.1016/j.neulet.2022.136851. Epub 2022 Aug 22.
Post-traumatic stress disorder (PTSD) has become epidemic following severely stressful incidents. Previous studies have shown that brain-derived neurotrophic factor (BDNF) has anxiolytic effects on various anxiety or depression disorders including PTSD. However, the detailed mechanisms of BDNF for treating PTSD were rarely investigated. In the current study, single-prolonged stress (SPS) was used as an animal model recapitulating specific aspects for a PTSD-like phenotype. The effects of BDNF on SPS-induced anxiety-like behaviors were investigated. We showed that the levels of BDNF in the cerebro-spinal fluid (CSF) were significantly reduced after the rats experienced SPS. The SPS-induced reductions of percentages of time spent in the central area to total time in the open field test, were dose-dependently mitigated after BDNF intracerebroventricular (i.c.v.) injections. BDNF i.c.v. administration also dose-dependently increased the preference of the light box in the light-dark box test. Both expressions of tyrosine kinase receptor B (TrkB) protein and mRNA in the prefrontal cortex (PFC) and amygdala were significantly increased after SPS challenges. BDNF i.c.v. administration attenuated these compensatory increases of TrkB. At last, the anxiolytic effects of BDNF on SPS model were also observed by using other two injection methods. These results inspired us to study that different administrations of BDNF were used in patients with PTSD in the future, in-depthly.
创伤后应激障碍(PTSD)在经历严重压力事件后已变得普遍。先前的研究表明,脑源性神经营养因子(BDNF)对各种焦虑或抑郁障碍(包括 PTSD)具有抗焦虑作用。然而,BDNF 治疗 PTSD 的详细机制很少被研究。在本研究中,采用单一延长应激(SPS)作为动物模型,重现 PTSD 样表型的特定方面。研究了 BDNF 对 SPS 诱导的焦虑样行为的影响。我们发现,大鼠经历 SPS 后,脑脊液(CSF)中的 BDNF 水平明显降低。BDNF 脑室(i.c.v.)注射可剂量依赖性减轻 SPS 诱导的旷场试验中中央区域时间百分比的减少。BDNF i.c.v. 给药还剂量依赖性地增加了在明暗箱测试中对光箱的偏好。SPS 挑战后,前额叶皮层(PFC)和杏仁核中的酪氨酸激酶受体 B(TrkB)蛋白和 mRNA 的表达均显著增加。BDNF i.c.v. 给药减轻了这些代偿性的 TrkB 增加。最后,还通过使用另外两种注射方法观察到 BDNF 对 SPS 模型的抗焦虑作用。这些结果启发我们将来在 PTSD 患者中深入研究不同的 BDNF 给药方法。