Phenylbutyric acid protects against spatial memory deficits in a model of repeated electroconvulsive therapy.
Repeated electroconvulsive therapy (rECT) is widely applied in the treatment of refractory depression. Among the side effects of rECT, memory impairment is noticeable and needs effective protection. In this study, by employing a recognized repeated electroconvulsive shock (rECS) rat model, we found that rECS induced the significant spatial memory retention deficits with the simultaneous decreases in long-term potential (LTP), enhanced excitable postsynaptic potentials (EPSP), population spike (PS) and input/output curve in perforant pathway-dentate gyrus (PP-DG), but had no obvious neuron loss or dentritic spine loss in the brain by Nissle or Golgi stainings. Furthermore, the increased synaptic proteins of NR2A/B, PSD93, PSD95, the immediate early gene c-Fos and CREB protein were detected in hippocampus of rECS rats. rECS was also found to cause enhanced axon reorganization in DG region of hippocampus by Timm staining. Intraperitoneal injection of phenylbutyric acid (PBA), an aromatic short chain fatty acid acting as a molecule chaperon, could prevent rats from the rECS-induced memory deficits and synaptic potential enhancement by decreasing the levels of the abnormally increased memory-associated proteins and enhanced axon reorganization in hippocampus. Our data suggested that PBA might be potentially used to attenuate the rECS-induced memory impairment.
Zhao-Hui
ZH
Yao
Xiang
X
Kang
Liu
L
Yang
Yi
Y
Niu
Ye
Y
Lu
Cheng-Xin
CX
Gong
Qing
Q
Tian
Department of Pathology and Pathophysiology, Key Laboratory of Neurological Diseases of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tianq@mail.hust.edu.cn.
Jian-Zhi
JZ
Wang
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy / Q000009:adverse effects*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D018696:Neuroprotective Agents; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid