Phenylbutyric Acid Protects Against Spatial Memory Deficits in a Model of Repeated Electroconvulsive Therapy
Zhao-Hui Yao, Xiang Kang, Liu Yang, Yi Niu, Ye Lu, Cheng-Xin Gong, Qing Tian and Jian-Zhi Wang
Affiliation: 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.
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.
Keywords: Repeated electroconvulsive shock, spatial memory, phenylbutyric acid.
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