Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Electroconvulsive seizures enhance autophagy signaling in rat hippocampus. 2431 74

Electroconvulsive therapy (ECT) is still the most effective strategy to treat severe and drug-resistant depressive disorders. Electroconvulsive seizure (ECS), which induces neuroplastic structural alterations and resilient behavioral changes in experimental animals, is the model of the ECT for human depression. ECT is typically administered three times per week for up to 4 weeks, while ECS treatments are administered daily for 10days. The increased expression of hippocampal brain-derived neurotrophic factor (BDNF) induced by antidepressive ECS treatment in experimental animals has been well documented. BDNF executes various neuroplastic functions by phosphorylating its high-affinity receptor, full-length TrkB, which has an intrinsic tyrosine kinase domain. However, the exact activation of BDNF/TrkB signaling following multiple ECS treatments has not been well elucidated. In epileptogenesis, conflicting effects of BDNF have been reported; while acute BDNF administration enhanced neuronal hyperexcitability and induced epileptiform activities, continuous BDNF infusion inhibited epileptogenesis. These conflicting results have been attributed to agonist-induced adaptive response of expressional down-regulation of the BDNF receptor. In the present study, using western blotting, we demonstrated increased phosphorylation as well as decreased expression of the full-length TrkB receptor (145kD) in both dorsal and ventral hippocampal regions of rats after a 10-day ECS treatment. The expression of mature BDNF (14kD) was up-regulated while that of proBDNF (32kD) remained unaltered in both hippocampal regions after the ECS treatment. Our results indicate that the hippocampal BDNF/TrkB signaling pathway is activated by multiple ECS treatments despite the ligand-induced down-regulation of the full-length TrkB receptor.
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PMID:Activated brain-derived neurotrophic factor/TrkB signaling in rat dorsal and ventral hippocampi following 10-day electroconvulsive seizure treatment. 2889 Mar 99