title: Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.
abstract: 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.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: 412557817@qq.com.
authors.forename: Su
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Qin
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology*; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy; D004597:Electroshock / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D007858:Learning / Q000187:drug effects; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D015742:Propofol / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D019208:Brain-Derived Neurotrophic Factor; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D015742:Propofol
keywords: Brain-derived neurotrophic factor; Electroconvulsive seizure; Memory; Propofol; Tissue plasminogen activator