title: Comparison of the neuropsychological mechanisms of 2,6-diisopropylphenol and N-methyl-D-aspartate receptor antagonist against electroconvulsive therapy-induced learning and memory impairment in depressed rats.
abstract: The present study aimed to examine the neurophysiological mechanisms of the 2,6-diisopropylphenol and N-methyl-D-aspartate (NMDA) receptor antagonist against learning and memory impairment, induced by electroconvulsive therapy (ECT). A total of 48 adult depressed rats without olfactory bulbs were randomly divided into six experimental groups: i) saline; ii) 10 mg/kg MK‑801; iii) 10 mg/kg MK‑801 and a course of ECT; iv) 200 mg/kg 2,6‑diisopropylphenol; v) 200 mg/kg 2,6‑diisopropylphenol and a course of ECT; and vi) saline and a course of ECT. The learning and memory abilities of the rats were assessed using a Morris water maze 1 day after a course of ECT. The hippocampus was removed 1 day after assessment using the Morris water maze assessment. The content of glutamate in the hippocampus was detected using high‑performance liquid chromatography. The expression levels of p‑AT8Ser202 and GSK‑3β1H8 in the hippocampus were determined using immunohistochemical staining and western blot analysis. The results demonstrated that the 2,6‑diisopropylphenol NMDA receptor antagonist, MK‑801 and ECT induced learning and memory impairment in the depressed rats. The glutamate content was significantly upregulated by ECT, reduced by 2,6‑diisopropylphenol, and was unaffected by the NMDA receptor antagonist in the hippocampus of the depressed rats. Tau protein hyperphosphorylation in the hippocampus was upregulated by ECT, but was reduced by 2,6‑diisopropylphenol and the MK‑801 NMDA receptor antagonist. It was also demonstrated that 2,6‑diisopropylphenol prevented learning and memory impairment and reduced the hyperphosphorylation of the Tau protein, which was induced by eECT. GSK‑3β was found to be the key protein involved in this signaling pathway. The ECT reduced the learning and memory impairment, caused by hyperphosphorylation of the Tau protein, in the depressed rats by upregulating the glutamate content.
authors.affiliation: Department of Anesthesiology, General Hospital of Beijing Military Area of PLA, Beijing 100700, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Tianjin Chest Hospital, Tianjin 300222, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Xue-Ning
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003866:Depressive Disorder / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D016291:Dizocilpine Maleate / Q000009:adverse effects* / Q000627:therapeutic use; D004565:Electroconvulsive Therapy; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D018698:Glutamic Acid / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000503:physiopathology; D007859:Learning Disabilities / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology; D015742:Propofol / Q000009:adverse effects* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D015742:Propofol