Effects of repeated electroconvulsive seizure on cell proliferation in the rat hippocampus

Abstract

Electroconvulsive therapy (ECT) is known as a successful treatment for severe depression. Despite great efforts, the biological mechanisms underlying the beneficial effects of ECT remain largely unclear. In this study, animals received a single, 10, or 20 applications of electroconvulsive seizure (ECS), and then cell proliferation and apoptosis were investigated in the subgranular zone (SGZ) of the dentate gyrus. We analyzed whether a series of ECSs could induce changes in the dentate gyrus in a dose-response fashion. A single-ECS seizure significantly increased cell proliferation in the SGZ by ∼2.3-fold compared to sham treatment. After 10 ECSs, a significant increase in cell proliferation was observed in the SGZ by ∼2.4-fold compared to sham treatment. Moreover, 10 ECSs induced a significant increase in cell proliferation by 1.3-fold compared to a single-ECS group. However, cell proliferation did not differ between the group with 20 ECSs and sham group. In addition, a significant increase in the number of apoptotic cells was found in the group with 10 ECSs, whereas no significant change in it was found in either a single ECS or 20 ECSs group compared to sham treatment. These findings indicate that the optimal number of treatments and duration of stimulation requires investigation. Further studies are needed to elucidate the intracellular mechanisms underlying both effective and excessive ECT.

The hippocampus and TNF: Common links between chronic pain and depression

“…Several case reports demonstrate electroconvulsive therapy effectiveness in the treatment of comorbid chronic pain and depression (Suzuki et al, 2009;Wasan et al, 2004). Interestingly, both electroconvulsive therapy and vagal nerve stimulation affect the hippocampus: clinical and experimental studies exploring the antidepressant and/or analgesic mechanism(s) of electroconvulsive therapy and vagal nerve stimulation action consistently demonstrate increased hippocampal BDNF production (Furmaga et al, 2012;Kuwatsuka et al, 2013;Li et al, 2007;Taliaz et al, 2013), CREB activation (Gebhardt et al, 2013), noradrenergic transmission (Manta et al, 2013) and neurogenesis (Gebhardt et al, 2013;Ito et al, 2010). Electroconvulsive therapy and vagal nerve stimulation mediate anti-inflammation processes that decrease levels of TNF␣ in blood serum/plasma (Bansal et al, 2012;Hestad et al, 2003).…”

Zinc and the ERK Kinases in the Developing Brain

“…Furthermore, protocols designed to induce depression-like behavior in mice and rats lead to decreased BDNF expression and ERK phosphorylation (Qi et al 2006; Smith et al 1995). Not only does zinc have antidepressant-like properties, but antidepressant therapies (including imipramine and electroconvulsive therapy) also stimulate an increase in zinc and BDNF concentrations along with increased ERK1/2 phosphorylation, and neural progenitor proliferation in the rat brain (Ito et al 2010; Nibuya et al 1995; Reus et al 2011; Schiavon et al 2010). In mice, the behavioral effects of antidepressant drugs require activation of the TrkB receptor (Saarelainen et al 2003).…”

Electroconvulsive stimulation transiently enhances the permeability of the rat blood-brain barrier and induces astrocytic changes

“…However, our method is not an animal model of ECT. We performed an excessive method, because effects of ECS on organic changes in the brain are relatively small [13]. Our model is a model of ECS-induced enhanced BBB permeability and would not be used to achieve an antidepressant effect.…”