Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways

作者：C. Anthony Altar, Pascal Laeng, Linda W. Jurata, Jeffrey A. Brockman, Andrew L. Lemire, Jeffrey Bullard, Yury V. Bukhman, Theresa Young, Vinod Charles, Michael G. Palfreyman · 发表于：Journal of Neuroscience · 年份：2004 · DOI：10.1523/jneurosci.5377-03.2004 · 被引用次数：316 · 研究领域：Electroconvulsive Therapy Studies、Transcranial Magnetic Stimulation Studies、Bipolar Disorder and Treatment

Electroconvulsive therapy (ECT) remains the treatment of choice for drug-resistant patients with depressive disorders, yet the mechanism for its efficacy remains unknown. Gene transcription changes were measured in the frontal cortex and hippocampus of rats subjected to sham seizures or to 1 or 10 electroconvulsive seizures (ECS), a model of ECT. Among the 3500-4400 RNA sequences detected in each sample, ECS increased by 1.5- to 11-fold or decreased by at least 34% the expression of 120 unique genes. The hippocampus produced more than three times the number of gene changes seen in the cortex, and many hippocampal gene changes persisted with chronic ECS, unlike in the cortex. Among the 120 genes, 77 have not been reported in previous studies of ECS or seizure responses, and 39 were confirmed among 59 studied by quantitative real time PCR. Another 19 genes, 10 previously unreported, changed by <1.5-fold but with very high significance. Multiple genes were identified within distinct pathways, including the BDNF-MAP kinase-cAMP-cAMP response element-binding protein pathway (15 genes), the arachidonic acid pathway (5 genes), and more than 10 genes in each of the immediate-early gene, neurogenesis, and exercise response gene groups. Neurogenesis, neurite outgrowth, and neuronal plasticity associated with BDNF, glutamate, and cAMP-protein kinase A signaling pathways may mediate the antidepressant effects of ECT in humans. These genes, and others that increase only with chronic ECS s...