Propofol ameliorates electroconvulsive shock-induced learning and memory impairment by regulation of synaptic metaplasticity via autophosphorylation of CaMKIIa at Thr 305 in stressed rats.
Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII.
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Li
L
Ren
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Fan
F
Zhang
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: 459910606@qq.com.
Su
S
Min
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Xuechao
X
Hao
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Peipei
P
Qin
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Xianlin
X
Zhu
D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D003863:Depression / Q000523:psychology*; D003866:Depressive Disorder / Q000628:therapy; D004565:Electroconvulsive Therapy / Q000379:methods; D004597:Electroshock / Q000379:methods; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002135:Calcium-Binding Proteins; C581829:Camk2n1 protein, rat; D002352:Carrier Proteins; D058785:GABA-A Receptor Agonists; D015742:Propofol
Ca(2+)/calmodulin-dependent kinase II; Electroconvulsive therapy; Learning; Memory; Metaplasticity; Propofol