title: Electroconvulsive seizures enhance autophagy signaling in rat hippocampus.
abstract: The putative antidepressive mechanisms of a series of electroconvulsive seizures (ECS) are the following: 1) downregulation of monoaminergic receptor expression in several brain regions, 2) upregulation of the expression of brain-derived neurotrophic factor (BDNF), and 3) increased neurogenesis in the hippocampus. In this study, we used Western blot techniques to present another mechanism in which ECS enhances the autophagy signaling that is involved in the machinery related to synaptic and neural plasticity. Antibodies for conjugated Atg5-Atg12 (58kD) and cleaved light chain protein 3-II (LC3-II; 14 kD) were used to detect autophagy signals. An antibody for cleaved caspase-3 (17 kD) was used to detect alterations in apoptotic signals. Mature BDNF (14kD) expression in the hippocampus was evaluated in order to qualify the effectiveness of the ECS or stress-loading treatment. While significantly increased autophagy signals and no increases in apoptotic signals were detected in the ECS-treated rat hippocampus, the reverse (increased apoptotic signals and no altered autophagy signals) was observed in stressed rat hippocampus. No neuronal cell loss but new mossy fiber sprouting has been reported to accompany multiple ECS treatments, and recent studies have revealed that autophagy processes regulate the number of specific neurotransmitter receptors and the plasticity of synaptic components. The present study illustrated the neuroplastic and neurotrophic profiles of ECS and the neurotoxic impact of severe stress loading on hippocampal regions. This is the first report to demonstrate increased autophagy signals in ECS-treated rat hippocampus and no alterations in autophagy signals in stress-loaded rat hippocampus.
authors: Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Hiroyuki
authors: H
authors: Otabe
authors: Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan. Electronic address: nibrin@ndmc.ac.jp.
authors: Masashi
authors: M
authors: Nibuya
authors: Department of Neurosurgery, Jichi Medical School, Shimotsuke, Tochigi, Japan.
authors: Kuniko
authors: K
authors: Shimazaki
authors: Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Hiroyuki
authors: H
authors: Toda
authors: Division of Behavioral Sciences, National Defense Medical College, Tokorozawa, Saitama, Japan; Military Medicine Research Unit, Test and Evaluation Command, Japan Ground Self Defense Force, Setagaya, Tokyo, Japan.
authors: Go
authors: G
authors: Suzuki
authors: Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Soichiro
authors: S
authors: Nomura
authors: Division of Behavioral Sciences, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Kunio
authors: K
authors: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D053148:Caspase 3 / Q000378:metabolism; D004597:Electroshock; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D000071187:Autophagy-Related Protein 5; D019208:Brain-Derived Neurotrophic Factor; D053148:Caspase 3; D008869:Microtubule-Associated Proteins; D011506:Proteins; C545865:Atg5 protein, rat; C526109:Anxa3 protein, rat
keywords: Apoptosis; Autophagy; Electroconvulsive seizure; Hippocampus; Single prolonged stress