Zhang Fan, Luo Jie, Min Su, Ren Li, Qin Peipei
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Brain Res. 2016 Jul 1;1642:43-50. doi: 10.1016/j.brainres.2016.03.020. Epub 2016 Mar 23.
This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression.
本研究调查了丙泊酚和电惊厥休克（ECS，动物体内电惊厥治疗（ECT）的类似物）对抑郁大鼠组织纤溶酶原激活物（tPA）及其抑制剂（PAI-1）以及脑源性神经营养因子前体（proBDNF）/成熟脑源性神经营养因子（mBDNF）比值的影响。ECT是治疗抑郁症的有效方法，但会导致认知缺陷。一些研究表明丙泊酚可改善ECT诱导的认知衰退，但其潜在分子机制仍不清楚。最近的证据发现mBDNF及其前体proBDNF与抑郁症和认知功能有关；它们对细胞功能产生相反的影响。慢性不可预测的轻度应激被广泛用于诱导啮齿动物的抑郁行为。本研究发现，抑郁症导致PAI-1表达增加、proBDNF/mBDNF比值上调，同时tPA水平降低、长时程增强（LTP）受损和认知衰退。抑郁大鼠接受ECS治疗后，proBDNF/mBDNF比值进一步上调，导致认知功能和海马LTP恶化。单独使用丙泊酚并不能逆转抑郁大鼠的这些变化，但与ECS联合使用时，它改善了认知功能，减轻了LTP损伤，下调了proBDNF/mBDNF比值，并增加了tPA表达。本研究结果表明，丙泊酚可改善ECT诱导的认知衰退，部分原因是通过调节proBDNF/mBDNF比值并逆转海马突触可塑性的过度变化，为proBDNF/mBDNF系统参与抑郁症的进展和治疗提供了新的证据。
