抑制 mGluR5 可改变前额叶皮层和海马体中的 BDNF/TrkB 和 GLT-1 表达，并改善大鼠 PTSD 样行为。
Inhibition of mGluR5 alters BDNF/TrkB and GLT-1 expression in the prefrontal cortex and hippocampus and ameliorates PTSD-like behavior in rats.
机构信息
Department of Medical Psychology and Ethics, School of Basic Medical Medicine Sciences, Cheeloo College of Medicine, Shandong University, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Department of Clinical Psychology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, 266035, Shandong, China.
出版信息
Psychopharmacology (Berl). 2023 Apr;240(4):837-851. doi: 10.1007/s00213-023-06325-7. Epub 2023 Feb 2.
RATIONALE AND OBJECTIVE
Post-traumatic stress disorder (PTSD) is a prevalent and debilitating psychiatric disorder. However, its specific etiological mechanism remains unclear. Previous studies have shown that traumatic stress changes metabotropic glutamate receptor 5 (mGluR5) expression in the hippocampus (HIP) and prefrontal cortex (PFC). More importantly, mGluR5 expression is often accompanied by alterations in brain-derived neurotrophic factor (BDNF). Furthermore, BDNF/tropomyosin-associated kinase B (TrkB) signaling plays multiple roles, including roles in neuroplasticity and antidepressant activity, by regulating glutamate transporter-1 (GLT-1) expression. This study aims to explore the effects of inhibiting mGluR5 on PTSD-like behaviors and BDNF, TrkB, and GLT-1 expression in the HIP and PFC of inevitable foot shock (IFS)-treated rats.
METHODS
Seven-day IFS was used to establish a PTSD rat model, and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) (10 mg/kg, intraperitoneal injection) was used to inhibit the activity of mGluR5 during IFS in rats. After modeling, behavioral changes and mGluR5, BDNF, TrkB, and GLT-1 expression in the PFC and HIP were examined.
RESULTS
First, the IFS procedure induced PTSD-like behavior. Second, IFS increased the expression of mGluR5 and decreased BDNF, TrkB, and GLT-1 expression in the PFC and HIP. Third, the mGluR5 antagonist blocked the above behavioral and molecular alterations.
CONCLUSIONS
mGluR5 was involved in IFS-induced PTSD-like behavior by changing BDNF, TrkB, and GLT-1 expression.
背景与目的
创伤后应激障碍（PTSD）是一种普遍且使人虚弱的精神障碍。然而，其具体的病因机制仍不清楚。既往研究表明，创伤性应激会改变海马（HIP）和前额叶皮质（PFC）中的代谢型谷氨酸受体 5（mGluR5）表达。更重要的是，mGluR5 的表达常伴随着脑源性神经营养因子（BDNF）的改变。此外，BDNF/原肌球蛋白相关激酶 B（TrkB）信号通过调节谷氨酸转运体-1（GLT-1）的表达，发挥多种作用，包括神经可塑性和抗抑郁活性。本研究旨在探讨抑制 mGluR5 对不可避免足底电击（IFS）处理大鼠 PTSD 样行为及 HIP 和 PFC 中 BDNF、TrkB 和 GLT-1 表达的影响。
方法
采用 7 天 IFS 建立 PTSD 大鼠模型，在 IFS 期间腹腔内注射 2-甲基-6-（苯乙炔基）-吡啶（MPEP，10mg/kg）抑制 mGluR5 活性。建模后，检测大鼠 PFC 和 HIP 中的行为变化以及 mGluR5、BDNF、TrkB 和 GLT-1 的表达。
结果
首先，IFS 程序诱发了 PTSD 样行为。其次，IFS 增加了 PFC 和 HIP 中 mGluR5 的表达，降低了 BDNF、TrkB 和 GLT-1 的表达。第三，mGluR5 拮抗剂阻断了上述行为和分子改变。
结论
mGluR5 通过改变 BDNF、TrkB 和 GLT-1 的表达参与了 IFS 诱导的 PTSD 样行为。
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