Electroconvulsive seizures stimulate the vegf pathway via mTORC1.

Electroconvulsive treatment (ECT) is considered the most effective treatment of depression. Recent studies demonstrate that electroconvulsive seizures (ECS), the animal variant of ECT, robustly stimulate hippocampal cell proliferation. However, the mechanisms underlying the cellular and molecular responses to ECS are not yet fully understood. A leading hypothesis of depression suggests that neurotrophic factors/growth factors play a critical role. Particularly the vascular endothelial growth factor (VEGF) is considered important, as it has been demonstrated that hippocampal VEGF expression is induced by ECS and that signaling through the VEGF receptor, Flk-1 (VEGFR2), is required for cell proliferation. VEGF expression is believed to be regulated by two distinct mTOR (mammalian Target of Rapamycin)-containing multiprotein complexes, mTORC1 and mTORC2, respectively. This study was undertaken to investigate the effect of ECS on the expression of VEGF, cognate receptors, mTORC1, and mTORC2 in the frontal cortex and the hippocampus. Using male Sprague-Dawley rats, the messenger RNA (mRNA) levels were measured by quantitative real time polymerase chain reaction (real-time qPCR) in three groups: Sham, acute (after one ECS), and repeated (ECS every day for 10 days). VEGF, VEGFR2, and components from mTORC1 were affected by repeated ECS, indicating that mediation of VEGF via mTORC1 is important for the effect of ECS.