Electroconvulsive seizure increases adult hippocampal angiogenesis in rats

Abstract

Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment-resistant depression. Despite the efficacy of electroconvulsive seizure as a non-chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20-30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation-3. There was also an induction of the angiogenesis markers alphaVbeta3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

“…This observation agrees with recent reports showing that fluoxetine or ECS treatment can stimulate the genesis of endothelial cells in both the hippocampus and the mPFC (Hellsten et al, 2004;Kodama et al, 2004;Madsen et al, 2005). Furthermore, this ECSinduced increase in endothelial cell proliferation is accompanied by increased angiogenesis in the hippocampus (Hellsten et al, 2005;Newton et al, 2006). The functional significance of these changes is not known, but they may be related to the 'vascular depression' hypothesis, which suggests that cerebrovascular disease may predispose, precipitate, or perpetuate at least some depressive syndromes, especially in geriatric patients (Alexopoulos et al, 1997).…”

Epileptiform Activity Induces Vascular Remodeling and Zonula Occludens 1 Downregulation in Organotypic Hippocampal Cultures: Role of VEGF Signaling Pathways

“…In a rat model of TLE with similar vascular remodeling, we found a significant upregulation of VEGF as reported in other models of seizures (Croll et al, 2004;Newton et al, 2006;Rigau et al, 2007;Nicoletti et al, 2008).…”

CREB Binding and Activity in Brain: Regional Specificity and Induction by Electroconvulsive Seizure

“…Acute ECS rapidly enhanced CREB occupancy and phosphorylation at promoters within hippocampus and frontal cortex, elevating CREB activity within multiple bioprocesses known to be induced by ECS, including trophic support, angiogenesis, neurogenesis, and plasticity ( Figure 2A; Supplement 9) (23,51). Increases in these bioprocesses in cortical and limbic brain regions have been implicated in the antidepressant actions of ECS and chemical antidepressants, suggesting that CREB plays an integral role in the molecular and behavioral adaptations to ECS (23,(52)(53)(54). While ECS enhanced CREB binding at select promoters in striatum, it had little effect on CREB phosphorylation in this region.…”