Electroconvulsive seizure increases adult hippocampal angiogenesis rats

Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 09/2006; 24(3):819-28. DOI: 10.1111/j.1460-9568.2006.04958.x
Source: PubMed


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.

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    • "Accumulating evidence from animal studies supports a neurotrophic effect of ECT. Pre-clinical studies have shown that electroconvulsive seizures lead to increased hippocampal neurogenesis (Scott et al., 2000) and angiogenesis (Newton et al., 2006), and enhanced glial proliferation in frontal cortex (Ongür et al., 2007). Over the past decades, different studies suggested that brainderived neurotrophic factor (BDNF) might be involved in the pathophysiology of mood disorders. "
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    ABSTRACT: Electroconvulsive therapy (ECT) is effective in treatment-resistant depression (TRD). It may act through intracellular process modulation, but its exact mechanism is still unknown. Animal research supports a neurotrophic effect for ECT. We aimed to investigate the association between changes in serum brain-derived neurotrophic factor (sBDNF) levels and clinical improvement following ECT in patients with TRD. Twenty-one patients with TRD (2 men, 19 women; mean age, 63.5 years; S.D., 11.9) were assessed through the Hamilton Depression Rating Scale (HDRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale, Severity (CGIs) before and after a complete ECT cycle. At the same time-points, patients underwent blood withdrawal for measuring sBDNF levels. ECT significantly reduced HDRS, BPRS, and CGIS scores, but not sBDNF levels. No significant correlation was found between sBDNF changes, and each of HDRS, BPRS, and CGIs score changes. sBDNF levels in TRD patients were low both at baseline and post-ECT. Our results do not support that improvements in TRD following ECT are mediated through increases in sBDNF levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Apr 2015
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    • "Environmental enrichment and running increase the density of endothelial cells in the hippocampus, whereas chronic stress and corticosterone decrease their density in rodents (Ekstrand et al. 2008; Van der Borght et al. 2009; Czéh et al. 2010; Kiuchi et al. 2012). Electroconvulsive seizures, which have a proven therapeutic application in the treatment of several depression diseases, increase vascular density in the DG and stratum lacunosum-moleculare of the adult hippocampus (Newton et al. 2006). Antidepressants increase the density of endothelial cells in the mid-DG of human brains (Boldrini et al. 2012). "
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    ABSTRACT: New neurons are continuously added to hippocampal circuitry involved with spatial learning and memory throughout life. These new neurons originate from neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). Recent studies indicate that vascular reconstruction is closely connected with neurogenesis, but little is known about its mechanism. We have examined vascular reconstruction in the hippocampus of adult mouse brain after the administration of the antidepressant fluoxetine, a potent inducer of hippocampal neurogenesis. The immunohistochemistry of laminin and CD31 showed that filopodia of endothelial cells sprouted from existing thick microvessels and often formed a bridge between two thick microvessels. These filopodia were frequently seen at the molecular layer and dentate hilus of the DG, the stratum lacunosum-moleculare of the CA1, and the stratum oriens of the CA3. The filopodia were exclusively localized along cellular processes of astrocytes, but such intimate association was not seen with cell bodies and processes of NSPCs. The administration of fluoxetine significantly increased vascular density by enlarging the luminal size of microvessels and eliminating the filopodia of endothelial cells in the molecular layer and dentate hilus. Treatment with fluoxetine increased the number of proliferating NSPCs in the granule cell layer and dentate hilus, and that of endothelial cells in the granule cell layer. Thus, antidepressant-induced vascular dynamics in the DG are possibly attributable to the alteration of the luminal size of microvessels rather than to proliferation of endothelial cells.
    Full-text · Article · Jun 2014 · Cell and Tissue Research
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    • "However, increased angiogenesis (and neurogenesis) was observed in SSRI-treated patients suffering from major depression [74]. Similarly, experimental ECS treatment was reported to promote the elongation of existing vessels and to increase their density in the stratum lacunosum moleculare (SLM), a subregion of the hippocampal molecular layer [76, 77]. However, within the granular layer of the dentate gyrus, that is, in the vicinity of stem and progenitor cell somas, we did not detect an increase of the blood vessel density upon experimental ECS treatments (Figure 5). "
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    ABSTRACT: Speculations on the involvement of hippocampal neurogenesis, a form of neuronal plasticity, in the aetiology of depression and the mode of action of antidepressive therapies, started to arise more than a decade ago. But still, conclusive evidence that adult neurogenesis contributes to antidepressive effects of pharmacological and physical therapies has not been generated yet. This review revisits recent findings on the close relation between the mode(s) of action of electroconvulsive therapy (ECT), a powerful intervention used as second-line treatment of major depression disorders, and the neurogenic response to ECT. Following application of electroconvulsive shocks, intricate interactions between neurogenesis, angiogenesis, and microglia activation, the hypothalamic-pituitary-adrenal axis and the secretion of neurotrophic factors have been documented. Furthermore, considering the fact that neurogenesis strongly diminishes along aging, we investigated the response to electroconvulsive shocks in young as well as in aged cohorts of mice.
    Full-text · Article · May 2014 · Neural Plasticity
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